Investigation of the effects of the chronic administration of some antihypertensive drugs on enzymatic and non-enzymatic oxidant/antioxidant parameters in rat ovarian tissue
Ministry of Health, Obstetrics and Gynecology Hospital, Iğdır, Turkey. Gynecological Endocrinology
(Impact Factor: 1.33).
11/2011; 27(11):895-9. DOI: 10.3109/09513590.2010.551564
In this study, effects of chronic antihypertensive drug (clonidine, methyldopa, amlodipine, ramipril, and rilmenidine) treatment on antioxidant-oxidant parameters were investigated in rat ovarian tissue.
Chronic drug administration for 30 days and at the end, biochemical examinations (total glutathione (tGSH), glutathione peroxidase (GPO), glutathione reductase (GR), glutathione s-transferase (GST), superoxide dismutase (SOD), nitric oxide (NO), catalase (CAT), malondialdehyde (MDA), and myeloperoxidase (MPO) analyses) were performed.
The levels of glutathione (GSH) and NO, and the activities of GPO, GR, GST, SOD, and CAT were measured the lowest in ramiprile group. Also in ramiprile group, the level of MDA and the activity of MPO was the highest.
We divided the drugs into four groups according to their biochemical side effect potentials in ovarian tissue: (I) Drugs which have no clear negative effect on ovarian tissue: clonidine, rilmenidine; (II) Drugs which have mild negative effect on ovarian tissue: methyldopa; (III) Drugs which have moderate negative effect on ovarian tissue: amlodipine; (IV) Drugs which have severe negative effect on ovarian tissue: ramipril. These data might be useful in the selection of the least toxic antihypertensive drug in pregnant and/or normal females.
Available from: Mustafa Talip Sener
- "In the experiment, clonidine (0.075 mg/kg), methyldopa
(100 mg/kg), amlodipine (2 mg/kg), ramipril
(2.5 mg/kg) and rilmenidine (0.5 mg/kg) were
administrated to female rats by gastric gavage for
30 days, once a day (12). Distilled water was given
to the healthy control group as vehicle, at the same
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In this study, we investigated the effects of treatment with chronic antihypertensive drugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine) on oxidant-antioxidant parameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examined histopathologically.
Materials and methods:
A total of 36 albino Wistar rats were divided into the following six groups: 0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg/kg ramipril group; 0.5 mg/kg rilmenidine group; and the healthy group. Rats underwent chronic drug administration for 30 days and at the end, biochemical and histopathological examinations were performed. All data were subjected to one-way ANOVA test.
We divided these drugs into the following three groups according to their effects on rat uteri: (I) mild negative effects (clonidine), (II) moderate negative effects (rilmenidine, methyldopa) and (III) drugs which had severe negative effects (amlodipine, ramipril).
These data may help with selection of antihypertensive drugs, in order to determine which drugs have the lowest toxicity in pregnant and non-pregnant (pre-pregnancy) women.
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ABSTRACT: To investigate the effects of metyrosine, lacidipine, clonidine, and moxonidine on the renal damage in rats with unilateral ureteral ligation by examining the histological evidence of parenchymal damage and tubular dilatation, as well as biochemical changes indicating cell membrane damage and DNA oxidation.
Thirty-six albino Wistar rats were randomly divided into six equal groups: a healthy (intact) group, a unilateral ureteral ligation (control) group, and four drug treatment groups given metyrosine (50 mg/kg), lacidipine (2 mg/kg), clonidine (0.075 mg/kg), or moxonidine (0.2 mg/kg), respectively, for 10 days. The latter five groups underwent ligation of the left ureter. Ten days after the operation, we removed both kidneys from each rat in the control and drug treatment groups for renal pathological and biochemical [malondialdehyde (MDA), total glutathione, 8-hydroxy-2-deoxyguanine (8-OH-Gua)] examinations. Spectrophotometric assays were used to detect the malondialdehyde and total glutathione levels of the renal tissue. High-performance liquid chromatography was used to measure the 8-hydroxy-2-deoxyguanine levels.
When the drug treatment groups were compared with the control group, the drug treatment groups' total glutathione level was higher and their malondialdehyde level was lower than that of the control group (P < 0.05), especially in the clonidine group (P < 0.0001). The 8-hydroxy-2-deoxyguanine levels of the drug treatment groups, except the lacidipine group, were significantly lower than that of the control group (P < 0.0001). There was no significant difference between the contralateral kidneys of the treatment groups and control group, according to the biochemical results. As revealed via light microscopy, clonidine and moxonidine treatment significantly reduced the tubular and glomerular damage, as well as the tubular dilation. The interstitial inflammation of the kidneys in the lacidipine group was higher than that of the other treatment groups. However, the apoptotic cell count was at a high level in both the lacidipine and metyrosine groups. The increase in the collagen content was most pronounced in the lacidipine and metyrosine groups. An examination of the contralateral kidneys showed no marked pathological findings.
The use of a direct or indirect α2-adrenergic receptor agonist for the temporary treatment of unilateral ureteral obstruction-induced renal damage may be important for preventing renal structural injury. A more advanced study is necessary to determine the mechanisms underlying the protective effects of these drugs with regard to renal damage in ureteral obstruction.
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ABSTRACT: Reperfusion has always been "the emergency intervention" to ischemic tissue. For a given period of time, tissue injury due to ischemia and reperfusion is more serious than injury due to ischemia only. Groups were as: Group 1: 25 µg/kg dexmedetomidine + ischemia/reperfusion group. Group 2: 10 mg/kg yohimbine +25 µg/kg dexmedetomidine + ischemia/reperfusion group. Group 3: Ischemia/reperfusion (control) group. Group 4: Healthy rats. Rat ovaries were exposed to a 3-hour ischemia and then reperfusion ensured for 2 hours. After ischemia/reperfusion, total glutathione, malondialdehyde, 8-hydroxyguanine levels and histopathological investigation were studied. The highest total glutathione and the lowest malondialdehyde and DNA damage levels were determined in dexmedetomidine group when compared to control group. The difference between yohimbine + dexmedetomidine and the control group was insignificant. Dexmedetomidine protects the ovarian tissue of the rat from I/R injury. It is hypothesized that this protective effect of dexmedetomidine is mediated by the α-2 adrenergic receptors. Dexmedetomidine could be useful for attenuation of tissue damage after I/R and prevention of I/R-related complications.
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