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Effect of an Aqueous Garlic Extract on Kidney Damage in an Experimental Model of Sepsis

Eect of an Aqueous Garlic Extract on Kidney Damage in an
Experimental Model of Sepsis
Sulu Sarımsak Ekstresinin Deneysel Sepsis Modelinde Böbrek Hasarı Üzerine Etkisi
Hazal İpekçi1, Tuğba Tunalı Akbay1, Göksel Şener2
1Department of Biochemistry, Marmara University School of Dentistry, İstanbul, Turkey
2Department of Pharmacology, Marmara University School of Pharmacy, İstanbul, Turkey
Correspondence Author/Sorumlu Yazar: Tuğba Tunalı Akbay E-mail/E-posta:
Received/Geliş Tarihi: 29.07.2016 Accepted/Kabul Tarihi: 27.09.2016 Available Online Date/Çevrimiçi Yayın Tarihi: 24.02.2017 DOI: 10.5152/clinexphealthsci.2017.140
©Copyright by 2017 Journal of Marmara University Institute of Health Sciences - Available online at
©Telif Hakkı 2017 Marmara Üniversitesi Sağlık Bilimleri Enstitüsü - Makale metnine web sayfasından ulaşılabilir
Sepsis is a condition characterized by a disseminated inammatory response triggered by a bacterial, viral, or fungal infection. In sepsis,
kidney injury frequently occurs as a complication (1). In this condition, kidney function decreases and the ion–water balance becomes
impaired (2).
It has been demonstrated that free radicals and the resultant oxidative stress play an important role in sepsis-induced multiorgan dam-
age (3, 4). Proinammatory markers of oxidative stress include cell and DNA damage, neutrophil recruitment, lipid peroxidation, and
protein oxidation (5). Therefore, antioxidant usage may increase survival rates by decreasing oxidative stress in sepsis (6).
Various studies have been conducted to understand the progression of septic kidney damage using animal models of sepsis. The cecal
ligation and perforation (CLP) model of polymicrobial peritonitis is frequently used in rats (7). To date, successful treatment strategies
have not been developed against sepsis-induced kidney damage. In the present study, the eect of prolonged 15 days AGE usage and
Amaç: Sepsis, patojenlere veya onların salgıladığı maddelere karşı verilen
sistemik inamatuvar bir yanıttır. Bu çalışmada sepsiste oluşan böbrek ha-
sarına karşı sulu sarımsak ekstresinin olası koruyucu etkisi incelenmiştir.
Yöntemler: Çalışmamızda sıçanlar; ‘kontrol’, ‘sepsis’, ‘sepsis+sarımsak’ ve
‘sepsis+ön-tedavili sarımsak’ grupları olmak üzere 4 gruba ayrılmıştır.
Sepsis modeli çekal ligasyon ve perforasyon yöntemi ile oluşturulmuştur.
‘Sepsis+ön-tedavili sarımsak’ grubuna sepsis oluşumundan 15 gün önce
başlanarak, 250 mg/kg/gün dozunda sulu sarımsak ekstresi oral yoldan uy-
gulanmıştır. ‘Sepsis+sarımsak’ grubunda ise tedavi sepsis uygulamasından
hemen sonra tek doz (250 mg/kg) olarak yapılmıştır. Sepsis oluşumundan
12 saat sonra bütün gruplardaki sıçanlar dekapite edilerek, böbrek dokula-
rı alınmıştır. Böbrek dokusunda, glutatyon (GSH) ve malondialdehit (MDA)
seviyeleri, süperoksit dismutaz (SOD), doku faktörü (TF), katalaz (CAT) ve
miyeloperoksidaz (MPO) aktivitesi tayin edilmiştir.
Bulgular: Sepsise bağlı olarak böbrek dokusunda artan MDA düzeyleri ve
MPO aktivitesi ile azalan GSH düzeyleri ve SOD ve CAT aktiviteleri sulu sa-
rımsak ekstresi ile geri çevrilmiştir. TF aktivitesi sepsiste değişmemiştir. Kı-
salmış pıhtı oluşum zamanı, artmış TF aktivitesini göstermektedir. Bu doğ-
rultuda ön-tedavili sepsis sarımsak grubunda TF aktivitesi artmıştır.
Sonuç: Sulu sarımsak ekstresi kullanımının yeni sepsis tedavi yöntemleri
geliştirilirken oksidan-antioksidan dengesi açısından dikkate alınması ge-
rektiğini düşünmekteyiz.
Anahtar Kelimeler: Sepsis, böbrek, sulu sarımsak ekstresi, oksidatif stres,
doku faktörü
Objective: Sepsis is a systemic inammatory response against pathogens
or substances secreted by pathogens. In this study, the potential protec-
tive eect of an aqueous garlic extract (AGE) against sepsis-induced kidney
Methods: Rats were divided into four groups: control, sepsis, sepsis+AGE-
garlic, and sepsis+pretreated garlic. Sepsis was induced using cecal ligation
and perforation. An AGE was orally administered to rats in the sepsis+pre-
treated garlic group at a dose of 250 (mg/kg/day) for 15 days prior to sepsis
induction. In rats in the sepsis+garlic group, the AGE was administered at a
single dose (250 mg/kg) immediately after sepsis induction. Twelve hours
after sepsis induction, all rats were decapitated and kidney tissues were
taken. Glutathione (GSH) and malondialdehyde (MDA) levels and super-
oxide dismutase (SOD), tissue factor (TF), catalase (CAT), and myeloperoxi-
dase (MPO) activities were determined in the kidney issue.
Results: Increased MDA levels and MPO activity and decreased GSH lev-
el and SOD and CAT activities due to sepsis were reversed by the AGE. TF
activity did not change in sepsis. Shortened clot formation time shows in-
creased TF activity. Accordingly, kidney TF activity signicantly increased in
mice in the pre-treated garlic group.
Conclusion: AGE usage should be considered in developing new sepsis
treatment strategies in terms of oxidant and antioxidant balance.
Keywords: Sepsis, kidney, aqueous garlic extract, oxidative stress, tissue
This study was presented as a poster at the 6th event of the Institute of Experimental Medicine (DETAE), 24-25 November, 2014, İstanbul, Turkey.
Bu çalışma 6. Deneysel Tıp Araştırma Enstitüsü (DETAE) Günleri’nde poster bildiri olarak sunulmuştur, 24-25 Kasım 2014, İstanbul, Türkiye.
Original Article /
Özgün Araştırma
single-dose aqueous garlic extract (AGE) against sepsis-induced
damages in kidney tissue was investigated.
Garlic, Allium sativum, has been widely used as a traditional medi-
cine for many years worldwide. It contains 1–3% of sulfur-containing
compounds (8). Allicin is the main sulfur-containing compound in
garlic (9). It has the ability to penetrate through membranes rapid-
ly, and it can react with thiol-containing proteins and enzymes (10).
There are many reports that show the antioxidant activity of garlic
and its constituents in vivo and in vitro, but its role in sepsis-induced
kidney damage has not been studied (11-14).
Wistar albino rats (200 to 250 g, either sex) were kept in a room where
the temperature was set to 22±2°C and relative humidity to 65–70%.
Light cycles were set as 12 h: 12 h light: dark. Standard rat chow was
used for feeding. The experimental protocol was approved by the
Marmara University Animal Care and Ethics Committee (Protocol
Number: 10.2015.mar)
AGE Preparation
Garlic was acquired from Kastamonu, Turkey. It was stored in dry and
light protected conditions. It means that standard controlled condi-
tions for plant. In a mortar, peeled garlic (30 g) was crushed with dis-
tilled water. It was decanted by pressing, and 60 mL of aqueous garlic
was extracted. One milliliter of AGE contained material from 500 mg
of garlic (1 mL of AGE extract contains 500 mg garlic, 500 mg/mL) (15,
16). The AGE was stored at 4°C.
Experimental Protocol and Sepsis Induction
Forty rats were equally divided into four groups: control (C), sepsis
(S), sepsis+garlic (S+AGE), and sepsis+pretreated garlic (S+pre-AGE).
Rats in the C and S groups were supplemented with saline and those
in the S+pre-AGE group were supplemented with AGE (250 mg/kg/
day orally) for 15 days prior to CLP. In rats in the sepsis+AGE group, a
single dose of garlic extract (250 mg/kg/day orally) was given imme-
diately after sepsis induction. In the sham-operated control groups
YES, after laparotomy, the cecum was manipulated but left intact
(without ligation or perforation). In the S group, rats underwent CLP
according to the method described by Fujimura et al. (17).
Minimal dissection was used for midline laparotomy; then, the ce-
cum was ligated just below the ileocecal valve with 3-0 silk ligatures.
Using an 18-gauge needle, the cecum was perforated at two loca-
tions and, the cecum was gently compressed until the feces were
entirely extruded. After feces extrusion, the incision was closed. All
rats were resuscitated with saline (3 mL/100 g body weight, subcu-
taneous.) at the end of the operation. Twenty-four hours after sepsis
induction, the rats were decapitated, and kidney tissues were taken.
Malondialdehyde (MDA) and glutathione (GSH) levels and superox-
ide dismutase (SOD), myeloperoxidase (MPO), catalase (CAT), and
tissue factor (TF) activities were determined in kidney tissue homog-
enates by the methods by Yagi (18), Beutler (19), Mylorie et al. (20),
Hillegas et al. (21), Aebi (22), and Ingram (23) respectively.
Statistical Analysis
Statistical analysis was performed using GraphPad Prism 5.0 (Graph-
Pad Software, San Diego, CA, USA), and all data were expressed as
mean±standard deviation. Data groups were compared with analysis
of variance (ANOVA) followed by Tukey ’s multiple comparison tests. A
p value of less than 0.05 was considered signicant.
MDA and GSH Levels
Kidney MDA levels signicantly increased in the S group in compari-
son with those in C group (Table 1). The increase seen in the S group
was in the S+pre-AGE group (Table 1). However, a single dose of AGE
administration did not signicantly change the MDA level in the S
Kidney GSH levels signicantly decreased in the S group in compar-
ison with those in the control group. Pre-AGE administration signi-
cantly increased GSH levels in the S group (Table 1).
Kidney SOD, CAT, and MPO Activities
Kidney SOD activity decreased in the S group in comparison to that
in the control group (Figure 1). A single dose of AGE administration
signicantly increased SOD activity in the S group (Figure 1).
Kidney CAT activity decreased in the S group but, this decrease was
not statistically signicant (Figure 2). Both AGE administrations sig-
nicantly increased CAT activity in S group (Figure 2). Kidney MPO
activity insignicantly increased in the S group (Figure 3). Both AGE
administrations signicantly decreased MPO activity in the S group
(Figure 3).
Kidney TF Activity
Tissue factor activity was expressed in seconds. Shortened clot for-
mation time shows increased TF activity. TF activity did not signi-
cantly change in the S group, but in S+pre-AGE group, TF activity sig-
nicantly increased (Table 2). A single dose of AGE administration did
not signicantly change TF activity in the S group (Table 2).
Clin Exp Health Sci 2017İpekçi et al. Garlic and Kidney Injury in Sepsis
(n=8) (n=8) (n=8) (n=8)
MDA (nmol MDA/g tissue) 63.41±3.32 112.3±8.,75 +++, ++ 67.92±8.04 95.65±3.83
GSH (µg GSH/g tissue) 138.0±8.30 105.3±3.82 +++, + 129.70±2.57 126.2±4.54
Values are given as mean±standard deviation (SD)
C: control; S: sepsis; S+pre-AGE: AGE administration 15 days prior to sepsis induction; S+AGE: single dose of AGE administration after sepsis induction; (èèè ): p<0.001
versus control group; (+): p<0.05 versus S+pre-AGE group
(++): p<0.01 versus S+pre-AGE group
Table 1. Malondialdehyde and glutathione levels in all groups
Garlic-derived allium derivatives have been shown to exert antibi-
otic, anticancer, antithrombotic, and lipid-lowering cardiovascular
eects (24). In the present study, renal pathologic changes induced
by oxidative damage due to experimental sepsis and the putative
protective roles of AGE against this damage were investigated. In
kidney tissue, AGE administration alleviated the sepsis-induced ox-
idative damage by signicantly decreasing the MDA level and MPO
activity and increasing the GSH level and SOD and CAT activities. Fur-
thermore, TF activity, which did not change in sepsis, increased by
AGE administration that was given 15 days prior to sepsis induction.
Sepsis-associated oxidative damage in kidney tissue was prevented
by the antioxidant properties of garlic.
Sepsis is an inammatory response that aects various organs and
systems; it also contributes to an inammatory response, microvas-
cular hypoperfusion, organ dysfunction, and increased mortality. In
sepsis, the kidney is subjected to inammatory cytokines and isch-
emia. Sepsis also causes widespread tubular cell apoptosis (25).
In sepsis, an increase in the production of ROS leads to multiorgan
dysfunction, mostly in the kidneys, lungs, liver, heart, and intestines.
These dysfunctions are known to result from bacterial toxins and en-
zymes, the eects of mediators, impaired perfusion, and disseminat-
ed intravascular coagulation (26).
Clin Exp Health Sci 2017 İpekçi et al. Garlic and Kidney Injury in Sepsis
(n=6) (n=8) (n=8) (n=8)
TF activity (sec.) 44.67±1.51 42.83±1.60 + 39.75±2.49 44.20±3.03
Values are given as mean±standard deviation (SD)
C: Control; S: sepsis; S+pre-AGE: AGE administration 15 days prior to sepsis induction; S+AGE: single dose of AGE administration after sepsis induction; TFa: tissue
factor activity; sec.: seconds (+): p<0.05 versus the S+pre-AGE group
Table 2. Kidney tissue factor activities in all groups
Figure 1. Superoxide dismutase activities in all groups
C: control; S: Sepsis; S+pre-AGE: AGE administration 15 days prior to
sepsis induction; S+AGE: Single dose of AGE administration after sepsis
induction; (ééé ): p<0.001 versus the control group, (•): p<0.05 versus
the S+AGE group
Figure 3. Myeloperoxidase activities in all groups
C: Control; S: Sepsis, S+pre-AGE: AGE administration 15 days prior to
sepsis induction; S+AGE: Single dose of AGE administration after sepsis
induction; (+): p<0.05 versus S+pre-AGE group; (•••): p<0.0001 versus
the S+AGE group
Figure 2. Catalase activities in all groups
C: Control; S: Sepsis; S+pre-AGE: AGE administration 15 days prior to
sepsis induction; S+AGE: single dose of AGE administration after sepsis
induction; (+): p<0.05 versus the S+pre-AGE group; (•): p<0.05 versus
S+AGE group
In the present study, the MDA level was signicantly increased in
kidney tissue. AGE administration prior to sepsis induction inhibit-
ed MDA elevations in kidney tissue, but single dose of AGE adminis-
tration did not signicantly change the increased kidney MDA level.
Restored control levels might be related to the maintained cellular
integrity that was achieved by AGE administration.
As an enzymatic antioxidant, SOD is particularly important for the
intracellular destruction of phagocytized bacteria and granulocyte
function (27). GSH, which is also a non-enzymatic antioxidant, pro-
tects tissues against oxidative stress (28). In our study, kidney tissue
GSH level and SOD and CAT activities decreased in the S group in
comparison to those in the control group. Pre-AGE administration
increased GSH level and CAT activity, while a single dose of AGE ad-
ministration was eective in increasing only SOD activity.
The heme enzyme MPO, found in neutrophils, uses a superoxide an-
ion to produce hypochlorous acid, which is the major oxidant for its
immune function (29). Thus, tissue-associated MPO activity is con-
sidered to correlate to the degree of inammatory damage. In the
present study, the increase in kidney MPO activity in the S group
compared to that in the C group might be related to neutrophil accu-
mulation in sepsis-induced oxidative injury. However, the decrease in
kidney MPO activity in both the S+AGE and S+pre-AGE groups might
be considered to explain the anti-inammatory eect of AGE.
Due to its receptor activity for factor VII, TF is the primary initiator of
the blood coagulation cascade, while also ensuring rapid hemosta-
sis in the case of organ damage (30). TF activity did not signicant-
ly change in the S group. As a shortened clot formation time shows
increased TF activity, AGE administration prior to sepsis induction
signicantly increased kidney TF activity. Increase in kidney TF activ-
ity with pre-treated AGE administration may help eliminate the sep-
sis-induced risk of bleeding in kidney tissues.
In conclusion, long-term AGE administration has great potential for
preventing the oxidation and inammation of the kidneys seen after
sepsis induction. The mechanism of this eect might be the mainte-
nance of cellular integrity by the AGE during sepsis.
Ethics Committee Approval: Ethics committee approval was received for
this study from the ethics committee on Research Animals of Marmara Uni-
versity (10.2015.mar).
Peer-review: Externally peer-reviewed.
Author contributions: Concept - T.A., G.Ş.; Design - T.A., G.Ş.; Supervision - T.A.,
G.Ş.; Resource - T.A., G.Ş., H.İ.; Materials - T.A., G.Ş., H.İ.; Data Collection and/or
Processing - T.A., G.Ş., H.İ.; Analysis and/or Interpretation - T.A., G.Ş., H.İ.; Liter-
ature Search - T.A., G.Ş., H.İ.; Writing - T.A., G.Ş., H.İ.; Critical Reviews - T.A., G.Ş.
Acknowledgements: The authors thanks to Marmara University Scientic
Research Project Department for supporting this study.
Conict of Interest: No conict of interest was declared by the authors.
Financial Disclosure: This study was supported by the Marmara University
Scientic Research Project Department (03.01.2014, SAG-C-YLP-030114-0008).
Etik Komite Onayı: Bu çalışma için etik komite onayı Marmara Üniversitesi
Hayvan Deneyleri Yerel Etik Kurulu’ndan alınmıştır (10.2015.mar).
Hakem Değerlendirmesi: Dış Bağımsız.
Yazar Katkıları: Fikir - T.A., G.Ş.; Tasarım - T.A., G.Ş.; Denetleme - T.A., G.Ş.; Kay-
naklar - T.A., G.Ş., H.İ.; Malzemeler - T.A., G.Ş., H.İ.; Veri Toplanması ve/veya işle-
mesi - T.A., G.Ş., H.İ.; Analiz ve/veya Yorum - T.A., G.Ş., H.İ.; Literatür taraması
- T.A., G.Ş., H.İ.; Yazıyı Yazan - T.A., G.Ş., H.İ.; Eleştirel İnceleme - T.A., G.Ş.
Teşekkür: Yazarlar, bu çalışmaya destek olduğu için Marmara Üniversitesi
Bilimsel Araştırma Projeleri Birimi’ne teşekkür ederler.
Çıkar Çatışması: Yazarlar çıkar çatışması bildirmemişlerdir.
Finansal Destek: Bu çalışma Marmara Üniversitesi Bilimsel Araştırma Projeleri
Birimi tarafından desteklenmiştir (03.01.2014, SAG-C-YLP-030114-0008).
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Clin Exp Health Sci 2017 İpekçi et al. Garlic and Kidney Injury in Sepsis
... 107 Moreover, in CLP-induced septic rats, aqueous garlic extract demonstrated ameliorative effects on kidney injury, because the garlic extract reversed the increased levels of MDA and MPO activity, as well as reversed the decreased levels of GSH and SOD and CAT activity that normally occur in sepsis. 108 It has also been previously reported that the extract of aged black garlic alleviates sepsis by suppressing the LPS-induced activation of MAPKs (ERK, JNK, and p38) and NF-κB, as well as downregulating the expression of COX-2, TNF-α, IL-6, and iNOs in LPSchallenged macrophages. 109 Allicin, a sulfide compound extracted from garlic bulbs, exerts its ameliorative effects on LPS-induced ALI by inhibiting the TLR4/MyD88/NF-kB signaling pathway, in addition to inhibiting the activity of caspase-3 and caspase-9 in the lung tissue of LPSchallenged rats. ...
... Moreover, in a study evaluating the effects of glycyrrhizin on LPS-activated macrophage-like RAW 264.7 cells, glycyrrhizin was reported to inhibit two major signaling pathways involved in the development of sepsis; specifically, the p38 MAPK/AP-1 and TLR4/ MD2-NF-κB signaling pathways. Blocking the TLR4/ MD2-NF-κB signaling pathway suppressed the release of TNF-α and IL-6, while blocking the p38 MAPK/AP-1 signaling pathway resulted in inhibition of HMGB1 in vivo secretion of TNFα, IL-6, and IL-1β attenuating the in vitro production of IL-Reduced the increased level of glutathione 2-Reduced the activity of CAT and SOD 3-Increased the level of MDA, tissue factor, and activity of MPO[108] LPS-challenged RAW 264.7 cells LPS-induced septicemia mice Suppressed the activation ERK, JNK, p38, and NF-κB decreased the expression of COX-2, TNF-α, IL-6, and iNOs[109] ...
Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper-production of pro-inflammatory mediators such as interleukin (IL)-1β, IL-6, tumor-necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro-inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well-known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti-inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life-threatening complications, such as multi-organ failure.
... SOD, an enzymatic antioxidant, is especially important in the intracellular destruction and phagocytosis of bacteria by granulocytes. GSH, a non-enzymatic antioxidant, plays an important role in protecting protein and lipid integrity and protecting tissues against oxidative stress [31,33]. Previous studies have determined that UF can modulate the antioxidant defense system by affecting antioxidant/oxidant parameters [19,34]. ...
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Sepsis is a pathophysiological event involving systemic inflammatory response syndrome, multiple organ failure syndromes, and tissue damage. Overproduction of free radicals as a result of tissue damage during sepsis contributes to cellular toxicity, organ failure, and even mortality. Antioxidants, which scavenge free radicals, play a protective role against various diseases. Previous studies have shown that umbelliferone (UF) has antioxidant and anti-inflammatory effects. Since oxidative stress is naturally associated with sepsis-induced organ dysfunction, the application of antioxidant compounds could potentially illuminate the pathophysiology of sepsis, which does not yet have an effective treatment. The sepsis model induced by cecal ligation and puncture (CLP) was applied to rats. Different doses of UF (10 mg/kg, 20 mg/kg, and 40 mg/kg) on oxidant-antioxidant in septic rats, mRNA of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1 its effects on expression levels were evaluated in lung, kidney, and liver tissues. When the lung, kidney, and liver tissues of septic rats were compared with those of the control group, it was found that UF administration increased dose-dependent superoxide dismutase activity and glutathione levels and significantly decreased malondialdehyde levels. The effects of UF administration on oxidative parameters were dose-dependent. The 40 mg/kg UF dose showed greater anti-oxidative properties than the 20 mg/kg and 10 mg/kg doses for all the evaluated parameters. Further, the TNF-α mRNA expression of the CLP +40 mg/kg group was reduced to a level comparable to that of the control group. UF has been found to be an effective molecule in reducing oxidative stress by supporting endogenous antioxidants and enhancing the scavenging effects of free radicals. The potent antioxidant property of UF may also be related to the suppression of the cytokine cascade during sepsis. The results suggest that UF administration may represent a new treatment for the prevention of lung, kidney and liver damage caused by septic conditions.
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Allicin (thio-2-propene-1-sulfinic acid S-allyl ester) is the main biologically active component of garlic clove extracts. Its biological activity was attributed to either antioxidant activity or thiol disulfide exchange. Antioxidant properties of both allicin and its precursor, alliin (+S-allyl-l-cysteine sulfoxide), were investigated in the Fenton oxygen-radical generating system [H2O2–Fe(II)]. Using the spin trapping technique and ESR, it was found that both compounds possessed significant antioxidant activity. The reaction between allicin and l-cysteine was studied by 1H and 13C-NMR, and a S-thiolation product, S-allylmercaptocysteine, was identified. Allicin irreversibly inhibited SH-protease papain, NADP+-dependent alcohol dehydrogenase from Thermoanaerobium brockii (TBAD), and the NAD+-dependent alcohol dehydrogenase from horse liver (HLAD). All the three enzymes could be reactivated with thiol containing compounds. Papain could be reactivated with glutathione, TBAD with dithiothreitol or 2-mercaptoethanol (2-ME) but not by glutathione, while HLAD could be reactivated only with 2-ME. This study demonstrates that in addition to its antioxidant activity, the major biological effect of allicin should be attributed to its rapid reaction with thiol containing proteins.
Due to its receptor activity for factor VII, tissue factor (TF) is primary initiator of the blood coagulation cascade and ensures rapid hemostasis in case of organ damage. Inflammatory cytokines, such as tumor necrosis factor-α or interleukins, strongly induce expression of both full-length TF as well as the alternatively spliced TF in endothelial and blood cells. Beyond its role in hemostasis, TF also has signaling activity and promotes pleiotropic inflammatory responses via protease-activated receptors in concert with other coagulation factors. Alteration of TF expression and TF alternative splicing provides an effective means to change the endothelial phenotype and modulate inflammatory responses of the vessel.
In Allium cepa (cv. Creamgold), A. cepa (cv. Bunching Onion), A. porrum (leek) and A. sativum (garlic), fructans were the only nonstructural carbohydrates detected apart from glucose, fructose and sucrose. No starch or members of the raffinose series of oligosaccharides were detected. Both cultivars of A. cepa, and A. porrum had fructan polymers of the same length. The maximum DP (degree of polymerization) detected was 12. However, maximum carbohydrate concentration occurred in DP5 for A. cepa (cv. Bunching Onion) and DP12 for A. porrum. A. sativum was different from the other species in that larger polymers were present, reaching a DP of 50. The trisaccharides, 1F-fructosylsucrose and 6G-fructosylsucrose were found in all species. A. cepa and A. sativum contained similar fructan: fructan frutosyltransferases. Enzymes from both plants transferred fructosyl residues from trisaccharide to form tetrasaccharide and sucrose as the major products. This self-transfer predominated even in the presence of higher molecular weight acceptor molecules.
One of the most frequent and serious complications to develop in septic patients is acute kidney injury (AKI), a disorder characterized by a rapid failure of the kidneys to adequately filter the blood, regulate ion and water balance, and generate urine. AKI greatly worsens the already poor prognosis of sepsis and increases cost of care. To date, therapies have been mostly supportive; consequently there has been little change in the mortality rates over the last decade. This is due, at least in part, to the delay in establishing clinical evidence of an infection and the associated presence of the systemic inflammatory response syndrome and thus, a delay in initiating therapy. A second reason is a lack of understanding regarding the mechanisms leading to renal injury, which has hindered the development of more targeted therapies. In this review, we summarize recent studies, which have examined the development of renal injury during sepsis and propose how changes in the peritubular capillary microenvironment lead to and then perpetuate microcirculatory failure and tubular epithelial cell injury. We also discuss a number of potential therapeutic targets in the renal peritubular microenvironment, which may prevent or lessen injury and/or promote recovery.
Sepsis is the most common and severe cause of morbidity and mortality among critically ill patients. Multiple organ dysfunction syndrome often complicates sepsis, leading to a worse prognosis that is proportional to the severity and number of damaged organs. Acute kidney injury (AKI) also complicates sepsis, with a linear relationship between the severity of kidney damage and sepsis prognosis. The management of sepsis and septic AKI involves intensive proactive preventive measures, medical and extracorporeal treatment of established sepsis, support of failing organs and rehabilitation of the residual effects left by this devastating syndrome. Unfortunately, although some innovations in the clinical management of sepsis are now available, their beneficial effects on renal function are still uncertain. The aim of this Review is to provide an update on the current state of interventions in sepsis-related AKI. Prevention, pharmacological support and extracorporeal blood purification for septic AKI will be reviewed and discussed.
The incidence of sepsis and acute kidney injury (AKI) are increasing in critically ill patients and both portend a higher risk of morbidity and death. Sepsis has consistently been shown to be a key contributing factor for the development of AKI. Numerous observational studies have found septic AKI to be highly common among the critically ill. Septic AKI patients are characterized by important differences in baseline demographics, acuity of illness and treatment intensity when compared with non-septic AKI. In particular, these patients are often older, have a higher prevalence of co-morbid illnesses, and are admitted for medical or emergency surgical indications. These patients show greater aberrancy in vital signs, laboratory parameters and need for vasoactive therapy and/or mechanical ventilation. Delays in initiation of appropriate antimicrobial therapy independently predict development of AKI in septic patients. Both delays to appropriate antimicrobials and initiation of renal support are also associated with higher mortality. Survival to ICU and/or hospital discharge for septic AKI patients is significantly lower when compared to patients with either non-septic AKI or sepsis alone. However, survivors of septic AKI show trends for greater rates of renal recovery and dialysis independence compared with non-septic AKI. The burden of septic AKI continues to increase and remains associated with an unacceptably high attributable morbidity and mortality. Accordingly, there is continued need to understand its epidemiology, not only to guide in management of these patients at the bedside, but also to stimulate advances in understanding its pathophysiology and in therapeutic interventions to potentially mitigate prognosis.