Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats (original) (raw)
Related papers
Melatonin attenuates acute renal failure and oxidative stress induced by mercuric chloride in rats
American Journal of Physiology-Renal Physiology, 2000
We evaluated the effect of melatonin (Mel), a potent scavenger of reactive oxygen species, in the course of HgCl2-induced acute renal failure. Rats received by gastric gavage 1 mg/kg of Mel ( n = 21) or vehicle ( n = 21), 30 min before the subcutaneous injection of HgCl2(2.5 mg/kg). Rats were killed at 24, 48, and 72 h, and plasma creatinine (Scr), renal histology, proliferative activity, apoptosis, and superoxide-producing cells were studied. We also determined the renal content of malondialdehyde (MDA) and glutathione (GSH) and the activities of glutathione peroxidase and catalase. Mel pretreatment (Mel plasma levels of 3.40 ± 3.15 μg/ml at the time of HgCl2injection) prevented the increment in Scrand reduced tubular necrosis from 41.0 ± 10.5 to 4.2 ± 5.1% of proximal tubules ( P < 0.01). Apoptosis and postnecrotic proliferative activity were twice more intense in the group untreated with Mel. Increment in renal content of MDA and decrease in GSH resulting from HgCl2toxicity we...
Melatonin ameliorates chronic renal failure-induced oxidative organ damage in rats
Journal of Pineal Research, 2004
Abstract: Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species (ROS). Melatonin, the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The aim of this study was to examine the role of melatonin in protecting the aorta, heart, corpus cavernosum, lung, diaphragm, and kidney tissues against oxidative damage in a rat model of CRF, which was induced by five of six nephrectomy. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or melatonin (10 mg/kg, i.p.) for 4 wk. CRF was evaluated by serum blood urea nitrogen (BUN) level and creatinine measurements. Aorta and corporeal tissues were used for contractility studies, or stored along with heart, lung, diaphragm, and kidney tissues for the measurement of malondialdehyde (MDA, an index of lipid peroxidation), protein carbonylation (PC, an index for protein oxidation), and glutathione (GSH) levels (a key antioxidant). Plasma MDA, PC, and GSH levels and erythrocytic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in CRF. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls (P < 0.05–0.001). Melatonin treatment of the CRF group restored these responses. In the CRF group, there were significant increases in tissue MDA and PC levels in all tissues with marked reductions in GSH levels compared with controls (P < 0.05–0.001). In the plasma, while MDA and PC levels increased, GSH, SOD, CAT, and GSH-Px activities were reduced. Melatonin treatment reversed these effects as well. In this study, the increase in MDA and PC levels and the concomitant decrease in GSH levels of tissues and plasma and also SOD, CAT, GSH-Px activities of plasma demonstrate the role of oxidative mechanisms in CRF-induced tissue damage, and melatonin, via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury. CRF-induced dysfunction of the aorta and corpus cavernosum of rats was reversed by melatonin treatment. Thus, supplementing CRF patients with adjuvant therapy of melatonin may have some benefit.
Protective effects of antioxidants on the experimental liver and kidney toxicity in mice
European Journal of …, 2008
Aim: Liver and kidney are exposed to a lot of oxidant substances that are both from exogen and endogen sources. The aim of this study was to investigate the antioxidant effects of C vitamine, Melatonine (MLT) and N-acetylcystein (NAC) in carbon tetrachlorur (CCl 4) induced oxidative stress in mouse. Methods: The study involved 6 groups; control group (Group 1), CCl 4 group (Group 2), CCl 4 + C vitamine group (Group 3), CCl 4 + MLT group (Group 4), CCl 4 + NAC group (Group 5) and combined (CCl 4 + C vitamine + MLT + NAC) group (Group 6) with each group containing 10 mice. Starting from the 4th day of the study 0,4 ml/kg CCl 4 were given intraperitoneally (i.p.) to all groups except the control group. In Groups 3, 4, 5 and 6; 150 mg/kg/day C vitamine, 10 mg/kg/day MLT, 150 mg/ kg/day NAC and C vitamine + MLT + NAC combination, respectively, were given for 7 days. The malondialdehyde (MDA) level and superoxide dismutase (SOD), glutatyon peroxidase (GSH-Px), catalase (CAT) and myeloperoxidase (MPO) activities were measured in the tissues of liver and kidney of the mice. Results: The MDA and MPO levels in the tissues of liver and kidney of the toxicity group (Group 2) were significantly higher than those of the control group (p<0.01), but the GSH-Px and CAT activities were significantly lower than those of the control group (p<0.01). Compared with the toxicity group; in groups 3, 5 and 6 liver MDA and MPO levels showed a significant decrease (p<0.05) while GSH-Px and SOD activities in group 4 and GSH-Px activity in group 5 showed a significant increase (p<0.05). In kidney, MDA levels in groups 3 and 5 and MPO levels in groups 4 and 6 showed a significant decrease (p<0.05). SOD in group 3; GSH-Px and CAT in group 4; GSH-Px, SOD and CAT in group 5 and SOD activities in group 6 showed a significant increase. Conclusion: The results showed that C vitamine therapy and the combined therapy were effective in preventing oxidative stress in both liver and kidney while MLT increased antioxidant enzyme activities more effectively. Furthermore, NAC was more effective in preventing oxidative stress and increasing antioxidant enzyme activities.
Nephroprotective effects of melatonin in hyperammonemia induced oxidative stress in Wistar rats
2015
The antioxidative action of melatonin on ammonium acetate induced hyperammonemia was studied in rats. In kidney tissue, the levels of thiobarbituri c acid reactive substances and lipid profile variables was observed to be increased significantly in ammonium acetate treated rats and decreased significantly in rats treated with melatonin and ammonium acetate. Enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase and non -enzymatic antioxidants such as reduced glutathione in kidney tissues decreased significantly in ammonium acetate treated rats and increased significantly in rats treated with melatonin and ammonium acetate. These biochemical alterations during melatonin treatment could be due to i) scavenging action of free radicals ii) induction of antioxidative enzymes that reduces the concentration of reactive oxygen species iii) inhibition of nitric oxide synthase Iv) cell membrane stabilization which assists them in reducing oxidative damage an...
Archives of Toxicology, 2007
This brief review summarizes some of the publications that document the preventive role of melatonin in kidney damage caused by carcinogens such as 2-nitropropane, arsenic, carbon tetrachloride, nitrilotriacetic acid and potassium bromate. Numerous chemicals generate excessive free radicals that eventually induce renal worsening. Melatonin partially or totally prevents free radical mediated tissue damages induced by many carcinogens. Protective actions of melatonin against the harmful eVects of carcinogens are believed to stem from its direct free radical scavenging and indirect antioxidant activities. Dietary or pharmacologically given melatonin may attenuate the oxidative stress, thereby mitigating the subsequent renal damage.
Dhaka University Journal of Pharmaceutical Sciences, 2018
Chemical or drug-induced kidney damage is increasing every year and the end-stage renal disease is becoming a burden for health care system of many countries. Oxidative stress may be a crucial pathway for the development of end-stage renal disease. Thus, natural antioxidant or plant-based therapy would be a better alternative to protect renal function against chemical-induced renal damage. To determine these aspects we evaluated renoprotective effects of M. charantia in carbon tetrachloride administered rats. A 10% w/w mixture of fresh fruits of M. charantia was given with the chow food every day to CCl4 treated rats. After fourteen days, all animals were sacrificed and the kidneys were examined to observe the possible protective effects of M. charantia against CCl4 induced toxicity. The CCl4 treated rats showed increased oxidative stress parameters and decreased antioxidant enzymes activities. Supplementation of 10% w/w M. charantia fruits in CCl4 administered rats prevented the ox...
Melatonin reduces oxidative stress induced by ochratoxin A in rat liver and kidney
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2001
. Melatonin MEL displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL Ž . on the oxidative stress induced by ochratoxin A OTA administration in rats was investigated. Four groups of 15 rats Ž . Ž . each were used: controls, MEL-treated rats 5 mgrkg body mass , OTA-treated rats 250 grkg and MEL q OTA-Ž . Ž . treated rats. After 4 weeks of treatment, the levels of malondialdehyde MDA , a lipid peroxidation product LPO were Ž . measured in serum and homogenates of liver and kidney. Also, the levels of glutathione GSH , and activities of Ž . Ž . Ž . Ž . glutathione reductase GR , glutathione peroxidase GSPx , superoxide dismutase SOD , catalase CAT and glu-Ž . tathione-S-transferase GST in liver and kidney were determined. In OTA-treated rats, the levels of LPO in serum and in both liver and kidney were significantly increased compared to levels in controls. Concomitantly, the levels of GSH and enzyme activities of SOD, CAT, GSPx and GR in both liver and kidney were significantly decreased in comparison with controls. In rats received MEL q OTA, the changes in the levels of LPO in serum and in liver and kidney were not statistically significant compared to controls. Concomitantly, the levels of GSPx, GR and GST activities in both liver and kidney tissues were significantly increased in comparison with controls. Similar increases in GSPx, GR and GST activities were also observed in MEL-treated rats when compared with controls. In conclusion, the oxidative stress may be a major mechanism for the toxicity of OTA. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and stimulation of GST activities. Thus, clinical application of melatonin as therapy should be considered in cases of ochratoxicosis. ᮊ
Amelioration of CCl4-induced nephrotoxicity by Oxalis corniculata in rat
Experimental and Toxicologic Pathology, 2013
CCl 4 induces oxidative stress in various tissues by altering antioxidant enzymes defense system. In this study we investigated the chemical composition and protective role of Oxalis corniculata methanol extract (OCME) on CCl 4-induced nephrotoxicity in rat. Presence of flavonoids, alkaloids, terpenoids, saponins, cardiac glycosides, phlobatannins and steroids was determined in OCME while tannins were absent. Total phenolic contents estimated were 7.76 ± 0.36 (mg gallic acid equivalents/g extract) while total flavonoid contents recorded were 6.92 ± 0.52 (mg rutin equivalents/g extract). Intraperitoneal injection of CCl 4 (1 ml/kg b.w., 20% in olive oil) once a day for seven days caused nephrotoxicity as evident by elevated levels of urinary specific gravity, RBCs, WBCs, creatinine, protein, urobilinogen and nitrite. Serum level of creatinine, urea, blood urea nitrogen were significantly increased while protein and creatinine clearance was decreased by CCl 4 treatment in kidney samples. Activity of antioxidant enzymes; catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glutathione concentration was decreased whereas lipid peroxidation and protein contents were increased along with histopathological injuries. Treatment with OCME caused significant recovery in changed parameters. It could be concluded that OCME has a protective role against CCl 4-induced oxidative stress in rat, due to antioxidant effects of phenolics.
Protective Effects of Melatonin and S-Methylisothiourea on Mechlorethamine Induced Nephrotoxicity
Journal of Surgical Research, 2012
Background. In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity. Materials and Methods. A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MECDMEL, and MECDSMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. Results. The tissue TNF-a, IL-1b, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-a and IL-1b levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue. Conclusions. Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have antiinflammatory properties, as well as anti-oxidant properties.