Mahaboob Khan

Publications

• 2.03

  Impact points

  Design, synthesis, and biological evaluation of a novel class of fluorescein-based N-glycosylamines.

  Mani Rajasekar, Sulaiman Mahaboob Khan, Sivasithamparam Niranjali Devaraj, Thangamuthu Mohan Das

  Carbohydrate research. 06/2011; 346(13):1776-85.

  A series of fluorescein-based N-glycosylamines was synthesized from the corresponding fluorescein amine and a partially protected d-glucose. The physiochemical investigation of these compounds by spectral and morphological studies reveals their gelation potential. The exclusive localization of fluor... [more] A series of fluorescein-based N-glycosylamines was synthesized from the corresponding fluorescein amine and a partially protected d-glucose. The physiochemical investigation of these compounds by spectral and morphological studies reveals their gelation potential. The exclusive localization of fluorescence in the cytoplasm through cell imaging studies reveals the anti-cancer potentials of N-glycosylamines.
• 2.46

  Impact points

  Methylated chrysin induces co-ordinated attenuation of the canonical Wnt and NF-kB signaling pathway and upregulates apoptotic gene expression in the early hepatocarcinogenesis rat model.

  Mahaboob S Khan, Devaraj Halagowder, S Niranjali Devaraj

  Chemico-biological interactions. 04/2011; 193(1):12-21.

  Hepatocellular carcinoma (HCC), a highly aggressive form of solid tumor, has been increasing in South East Asia. The lack of effective therapy necessitates the introduction of novel chemopreventive strategies to counter the substantial morbidity and mortality associated with the disease. Recently, w... [more] Hepatocellular carcinoma (HCC), a highly aggressive form of solid tumor, has been increasing in South East Asia. The lack of effective therapy necessitates the introduction of novel chemopreventive strategies to counter the substantial morbidity and mortality associated with the disease. Recently, we reported that dimethoxy flavone (DMF), a methylated flavone derived from chrysin, significantly suppressed the development of preneoplastic lesions induced by N-nitrosodiethylamine (DEN) in rats, although the mechanism of action was not known. In the present study, we have investigated the effects of DMF administration on gene expression changes related to the inflammation-mediated NF-kB pathway, Wnt pathway and apoptotic mediators in DEN-induced preneoplastic nodules. There was a significant increase in inflammatory markers like cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and a decrease in apoptotic mediators like p53, caspase-3 and bax in DEN-treated rats when compared to the control group. Activation of NF-kB was noticed by an elevated expression of nuclear protein expression of NF-kB and cytoplasmic phospho-IkBαSer(32/36) in the same animals. Likewise, upregulation of canonical Wnt pathway was noticed by elevated expression of nuclear protein levels of phospho-β-cateninThr(393) and cytoplasmic casein kinase-2 (CK2), Dvl2 and cyclin D1 levels, along with a simultaneous decrease in expression of phospho-GSK3β(Ser9). Dietary DMF (100mg/kg) administration inhibited liver nodule incidence and multiplicity by 82% and 78%, respectively. DMF also reversed the activation of NF-kB and Wnt pathway as shown by the decrease in protein expression of several proteins. Results of the present investigation provide evidence that attenuation of Wnt pathway and suppression of inflammatory response mediated by NF-kB could be implicated, in part, in the chemopreventive effects of methylated flavone. Therefore, the present findings hold great promise for the utilization of DMF as an effective chemotherapeutic agent in treating early stages of liver cancer.
• 3.36

  Impact points

  Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats.

  Mahaboob S Khan, Halagowder Devaraj, Niranjali Devaraj

  Toxicology and applied pharmacology. 02/2011; 251(1):85-94.

  Flavonoids possess strong anti-oxidant and cancer chemopreventive activities. Chrysin (5,7-dihydroxyflavone) occurs naturally in many plants, honey, and propolis. In vitro, chrysin acts as a general anti-oxidant, causes cell cycle arrest and promotes cell death. However, the mechanism by which chrys... [more] Flavonoids possess strong anti-oxidant and cancer chemopreventive activities. Chrysin (5,7-dihydroxyflavone) occurs naturally in many plants, honey, and propolis. In vitro, chrysin acts as a general anti-oxidant, causes cell cycle arrest and promotes cell death. However, the mechanism by which chrysin inhibits cancer cell growth and the subcellular pathways activated remains poorly understood. Effect of dietary supplementation with chrysin on proliferation and apoptosis during diethylnitrosamine (DEN)-induced early hepatocarcinogenesis was investigated in male Wistar rats. To induce hepatocarcinogenesis, rats were given DEN injections (i.p., 200 mg/kg) three times at a 15 day interval. An oral dose of chrysin (250 mg/kg bodyweight) was given three times weekly for 3 weeks, commencing 1 week after the last dose of DEN. Changes in the mRNA expression of COX-2, NFkB p65, p53, Bcl-xL and β-arrestin-2 were assessed by quantitative real-time PCR. Changes in the protein levels were measured by western blotting. Chrysin administration significantly (P<0.001) reduced the number and size of nodules formed. Also, a significant (P<0.01) reduction in serum activities of AST, ALT, ALP, LDH and γGT was noticed. Expression of COX-2 and NFkB p65 was significantly reduced whereas that of p53, Bax and caspase 3 increased at the mRNA and protein levels. Likewise, a decrease in levels of β-arrestin and the anti-apoptotic marker Bcl-xL was also noted. These findings suggest that chrysin exerts global hepato-protective effect and its chemopreventive activity is associated with p53-mediated apoptosis during early hepatocarcinogenesis.
• 2.11

  Impact points

  Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-nitrosodiethylamine in rats.

  Mahaboob S Khan, Devaraj Halagowder, S Niranjali Devaraj

  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 10/2010; 49(1):173-8.

  The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200 mg/kg bodyweight) interspersed by 2 weeks with or without an or... [more] The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200 mg/kg bodyweight) interspersed by 2 weeks with or without an oral dose of dimethoxy flavone (DMF 100 mg/kg bodyweight), 2 weeks after DEN initiation. The number of GST-Pi positive foci and proliferating cell nuclear antigen (PCNA)-positive cells were significantly suppressed by the administration of DMF. Real-time RT-PCR analysis revealed that DMF treatment increased mRNA expression levels of apoptotic proteins p53 and fas, cell cycle regulatory proteins chek 2, cdkn1a, rad 50, anti-inflammatory protein pparg whereas the mRNA expression levels of bcl-2 and prdx-2 were decreased compared to mRNA levels in DEN-treated group. Therefore, we propose that DMF partially suppresses the formation of preneoplastic lesions in rats following DEN exposure by regulating anti-inflammatory and apoptosis-promoting events and restoring the cellular redox balance altered by DEN.
• 1.95

  Impact points

  Malnutrition, anthropometric, and biochemical abnormalities in patients with diabetic nephropathy.

  Mahaboob S Khan, Sandhu Chandanpreet, Krishan Kewal, D'Cruz Sanjay, Kashyap Jeet Ram, Sachdeva Atul

  Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 08/2009; 19(4):275-82.

  OBJECTIVE: Malnutrition is widely prevalent in patients with chronic kidney disease. Our primary objective was to assess the utility of subjective global assessment (SGA) as an indicator of malnutrition in patients with diabetic nephropathy. DESIGN: This pilot study evaluated the extent of malnutrit... [more] OBJECTIVE: Malnutrition is widely prevalent in patients with chronic kidney disease. Our primary objective was to assess the utility of subjective global assessment (SGA) as an indicator of malnutrition in patients with diabetic nephropathy. DESIGN: This pilot study evaluated the extent of malnutrition, using a combination of SGA, anthropometric, and biochemical parameters. SETTING: Malnutrition, although commonly noticed in patients during routine clinical observation of diabetic nephropathy patients, has not been estimated. Moreover, there is no single "gold standard" method to identify malnutrition. PATIENTS: The SGA method was performed to evaluate nutritional status in 40 patients with diabetic nephropathy (23 men and 17 women) examined consecutively in the out patient department of Government Medical College and Hospital (Chandigarh, India). Patients with kidney disease not attributable to diabetes, and with conditions leading to acute morbidity such as infections, elevated body temperature, respiratory and gastrointestinal distress, or wounds, were excluded. MAIN OUTCOME MEASURES: Anthropometric parameters such as body mass index, triceps skinfold (TSF), biceps skinfold (BSF), midarm circumference (MAC), and midarm muscle circumference (MAMC), along with biochemical parameters such as hemoglobin, fasting blood sugar, serum albumin, and lipid profile, were measured. RESULTS: Malnutrition was identified in 63% of patients: mild to moderate in 48%, and severe in 15%. The measured parameters showed no significant gender-based differences. In SGA grade C patients (severely malnourished), TSF, MAC, and MAMC were significantly reduced. Biochemical parameters did not show any significant change across nutritional grades, except for hemoglobin, which showed a significant reduction with advanced malnutrition. CONCLUSIONS: Nutritional status as determined by SGA is a useful and reliable index for identifying patients at risk for malnutrition. Our data confirm that a high degree of malnutrition was prevalent in patients with diabetic nephropathy, as shown by anthropometric and biochemical variables. Therefore, we suggest that these parameters be integrated in regular assessment to determine malnutrition.

• Sub acute oral toxicity of Chlorpyriphos and protective effect of green tea extract

  Mahaboob S Khan, Gurjot Kour

  Pesticide Biochemistry and Physiology. 09/2007; 89:118-123.
• 2.54

  Impact points

  Pesticide-induced alteration in mice hepato-oxidative status and protective effects of black tea extract.

  S Mahaboob Khan, R C Sobti, Lincee Kataria

  Clinica chimica acta; international journal of clinical chemistry. 09/2005; 358(1-2):131-8.

  BACKGROUND: This study investigates the role of black tea extract in protection against oxidative damage induced in mice by a subacute oral dose of a combination of pesticides. METHODS: Liver damage markers like amino-acid transferases and alkaline phosphatase, oxidative damage markers indicating ex... [more] BACKGROUND: This study investigates the role of black tea extract in protection against oxidative damage induced in mice by a subacute oral dose of a combination of pesticides. METHODS: Liver damage markers like amino-acid transferases and alkaline phosphatase, oxidative damage markers indicating extent of lipid peroxidation, host antioxidant reserve indicators like reduced glutathione (GSH) and total thiol levels, GSH-dependent enzyme activities viz., glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) superoxide dismutase (SOD) and catalase (CAT) were measured by spectrophotometric techniques in four different groups namely (1) control, (2) black tea extract, (3) pesticide alone and (4) pretreatment with black tea extract followed by pesticide treatment. RESULTS: Following exposure to pesticides lipid peroxidation was increased compared to that in the control [0.50+/-0.083 (mean+/-S.E.) vs. 0.21+/-0.02 micromol/mg protein, p<0.001]. Moreover, levels of antioxidants like GSH and total thiol were also significantly decreased in comparison to control, e.g., GSH [5.16+/-0.78 vs. 6.96+/-1.35 micromol/mg protein, p<0.001], total thiol [19.3+/-2.74 vs. 26.15+/-2.8 micromol/mg protein, p<0.001]. In addition, the activities of antioxidant enzymes like GPx, GST, GR, SOD and catalase were also likewise diminished by oxidant damage. Treatment with aqueous black tea extract significantly protects the liver tissue from the oxidative damage and shifts the trend towards amelioration and replenishment of the antioxidant status. CONCLUSIONS: The active components present in natural extracts like that of black tea can be very effective in perhaps reducing the extent of injury and in overcoming oxidant damage caused by exposure to environmental agents like pesticides.

• Pesticide-induced alteration in mice hepato-oxidative status and protective effects of black tea extract

  S. Mahaboob Khan, R.C. Sobti, Lincee Kataria

  Clinica Chimica Acta.

  BackgroundThis study investigates the role of black tea extract in protection against oxidative damage induced in mice by a subacute oral dose of a combination of pesticides.MethodsLiver damage markers like amino-acid transferases and alkaline phosphatase, oxidative damage markers indicating extent ... [more] BackgroundThis study investigates the role of black tea extract in protection against oxidative damage induced in mice by a subacute oral dose of a combination of pesticides.MethodsLiver damage markers like amino-acid transferases and alkaline phosphatase, oxidative damage markers indicating extent of lipid peroxidation, host antioxidant reserve indicators like reduced glutathione (GSH) and total thiol levels, GSH-dependent enzyme activities viz., glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) superoxide dismutase (SOD) and catalase (CAT) were measured by spectrophotometric techniques in four different groups namely (1) control, (2) black tea extract, (3) pesticide alone and (4) pretreatment with black tea extract followed by pesticide treatment.ResultsFollowing exposure to pesticides lipid peroxidation was increased compared to that in the control [0.50 ± 0.083 (mean ± S.E.) vs. 0.21 ± 0.02 μmol/mg protein, p < 0.001]. Moreover, levels of antioxidants like GSH and total thiol were also significantly decreased in comparison to control, e.g., GSH [5.16 ± 0.78 vs. 6.96 ± 1.35 μmol/mg protein, p < 0.001], total thiol [19.3 ± 2.74 vs. 26.15 ± 2.8 μmol/mg protein, p < 0.001]. In addition, the activities of antioxidant enzymes like GPx, GST, GR, SOD and catalase were also likewise diminished by oxidant damage. Treatment with aqueous black tea extract significantly protects the liver tissue from the oxidative damage and shifts the trend towards amelioration and replenishment of the antioxidant status.ConclusionsThe active components present in natural extracts like that of black tea can be very effective in perhaps reducing the extent of injury and in overcoming oxidant damage caused by exposure to environmental agents like pesticides.
• 1.52

  Impact points

  Protective effect of black tea extract on the levels of lipid peroxidation and antioxidant enzymes in liver of mice with pesticide-induced liver injury.

  S Mahaboob Khan

  Cell biochemistry and function. 24(4):327-32.

  Sub-acute hepatotoxicity was induced in mice by exposure to pesticides. The effect of pretreatment with aqueous black tea extract on lipid peroxidation and antioxidants in the liver was investigated. Administering a combination dose of chlorpyriphos and cypermethrin (20 mg kg(-1) each) on alternate ... [more] Sub-acute hepatotoxicity was induced in mice by exposure to pesticides. The effect of pretreatment with aqueous black tea extract on lipid peroxidation and antioxidants in the liver was investigated. Administering a combination dose of chlorpyriphos and cypermethrin (20 mg kg(-1) each) on alternate days over a 15-day period to male mice resulted in induction of sub-acute toxicity as reflected by elevated levels of liver damage marker enzymes alkaline phosphatase(ALP), aspartate transaminase(AST) and alanine transaminase(ALT). Significantly elevated levels of lipid peroxidation were observed in the experimental group (group III) as compared with control mice. Decreased activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total thiol, glutathione peroxidase (GPx), glutathione reductase(GR) and glutathione-S-transferase (GST) were also observed in pesticide-treated as compared to control mice. Aqueous black tea extract was given as a pretreatment to group IV mice at a dose of 200 mg ml(-1) polyphenols before the pesticide dose, which significantly decreased the levels of lipid peroxidation and significantly elevated the activities of SOD, CAT, GSH, total thiol, GPx, GR and GST in liver to levels similar to the controls. Thus, the data offer support for the claim that the central mechanism of pesticide action occurs via changes in cellular oxidative status and shows conclusively that supplementation with black tea extract protects against the free radical-mediated oxidative stress in hepatocytes of animals with pesticide-induced liver injury.