Nigar Vardi

Potent protective effect of apricot and β-carotene on methotrexate-induced intestinal oxidative damage in rats

Several studies have well confirmed the contribution of oxidative stress in the pathogenesis of methotrexate (MTX)-induced damage in the small intestine. Many agents have been tried experimentally to reduce or inhibit the oxidative stress. To our knowledge, there is no study about apricot consumption on the MTX-induced damage in the small intestine. The aim of this study was to determine the possible protective effects of apricot and beta-carotene on MTX-induced intestinal damage in rats. The rats were randomly divided into seven groups as follows; I-control group; II-apricot group; III-beta-carotene group; IV-MTX group; V-apricot+MTX group; VI-beta-carotene+MTX group and VII-apricot+beta-carotene+MTX group. In the MTX group; fusion and shortening in the villus, epithelial desquamation, crypt loss, inflammatory cell infiltration in the lamina propria, goblet cell depletion and microvillar damage were observed in the small intestine. Parallel to histological results, malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were found to be increased, whereas superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP-x) activities and glutathione (GSH) content were decreased in the MTX group. However, single or combined application of apricot and beta-carotene ameliorated all of these hazardous effects in antioxidant system in MTX-treated groups. In conclusion, our results demonstrate that apricot and/or beta-carotene treatment may protect the impairment of oxidative stress and ameliorate MTX-induced intestine damage at biochemical and histological levels.

Carbon tetrachloride-induced nephrotoxicity and protective effect of betaine in Sprague-Dawley rats.

OBJECTIVES To observe the changes in the antioxidative defense enzymes and to detect the alterations of renal microscopy after carbon tetrachloride (CCl4) administration in rats and to investigate the possible protective effects of betaine against CCl4-induced renal damage. METHODS Thirty-two adult Sprague-Dawley rats were divided into four groups as follows: control group, betaine group, CCl4 group, and CCl4 + betaine group. CCl4 was given subcutaneously at 1 mL/kg. In the CCl4 + betaine group, rats were pretreated with betaine, then exposed to CCl4 at the same dose. Betaine group rats received concentrated betaine solution. The rats were killed and the kidneys taken for enzyme analyses and histologic examination. Glutathione peroxidase, superoxide dismutase, and catalase activities were measured in right kidney homogenates. Left kidneys were processed for light microscopic evaluation. RESULTS In the CCl4-treated group, significant increases in kidney superoxide dismutase and catalase activities and significant decrease in glutathione peroxidase activity were observed (P <0.01). These changes were found to be normalized in the CCl4 + betaine group. Betaine did not change the enzyme activities. Exposure to CCl4 resulted in glomerular and tubular alterations in the renal cortex. These alterations were found to be prevented by betaine pretreatment. CONCLUSIONS These results indicate that exposure to CCl4 leads to renal damage in rats and betaine exerts an improvement on nephrotoxic effects of CCl4.

Physiological and pharmacological concentrations of melatonin protect against cisplatin-induced acute renal injury

Abstract: Abstract: Cisplatin [cis‐diaminedichloroplatinum(II), CDDP] is a widely used antineoplastic drug. However, it has major side‐effects such as acute tubular necrosis (ATN). There are a number of studies concerning the role of reactive oxygen radical species in the pathophysiology of CDDP‐dependent ATN. Several antioxidant agents have been reported to prevent this side‐effect but there is no study regarding the protective action of either physiological or pharmacological concentrations of melatonin. Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. We investigated the effects of melatonin on CDDP‐induced changes of renal malondialdehyde (MDA), a lipid peroxidation product, and blood urea nitrogen (BUN) and serum creatine (Cr). The morphological changes in kidney were also examined using light microscopy. The rats were divided into two groups: pinealectomized (Px) and sham‐operated (non‐Px). Both CDDP and melatonin were administered to all groups. MDA levels were found to be higher in Px than non‐Px animals. CDDP administration to Px or non‐Px rats increased renal MDA levels and melatonin administration either before or after CDDP injection caused significant decreases in MDA in kidney compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr did not change as a result of any treatment. Morphological tubule damage because of CDDP was more severe in the renal cortex than in the medulla. The damage to the kidney induced by CDDP was reversed by melatonin. The results show that pharmacological and physiological concentrations of melatonin reduce CDDP‐induced renal injury.

Amikacin-induced acute renal injury in rats: protective role of melatonin

Abstract: It is well established that some agents such as aminoglycosides generate free oxygen radicals, leading to an increased oxireductase production, which in turn increases tissue toxicity. The aim of this study is to test whether melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant and free radical scavenger, reduces the nephrotoxicity caused by amikacin (AK). Herein, we investigated the physiologic and pharmacological role of melatonin in influencing AK‐induced nephrotoxicity. For this, pinealectomized (Px) and sham operated (non‐Px) rats were used. Both AK and melatonin were administered to all groups. We investigated the effects of melatonin on AK‐induced changes in levels of malondialdehyde (MDA), a lipid peroxidation product, glutathione (GSH), an antioxidant whose levels are influenced by oxidative stress, and blood urea nitrogen (BUN) and serum creatine (Cr) levels. Morphologic changes in the kidney were also examined by using light microscopy. MDA levels were found to be higher in Px than in non‐Px AK‐treated animals. Melatonin administration to Px rats reduced MDA levels. In relative to non‐Px rats, Px animals treated with AK had significantly lower GSH concentrations while melatonin administration elevated GSH levels in the kidney; however, this stimulatory effect of melatonin was not observed in non‐Px AK‐treated rats. Treatment with AK alone resulted in significantly higher plasma Cr and BUN levels. Repeated administration of melatonin prevented the AK‐induced elevation of plasma Cr and BUN levels. Morphologic damage to renal tubules as a result of AK was more severe in the renal cortex than in the medulla. The damage to the kidney induced by AK was reversed by melatonin in the Px rats. In conclusion, these results show that physiologic melatonin concentrations are important in reducing AK‐induced renal damage, while pharmacologic concentrations of melatonin did not add to the beneficial effect.

Ischemia-reperfusion leads to depletion of glutathione content and augmentation of malondialdehyde production in the rat heart from overproduction of oxidants: Can caffeic acid phenethyl ester (CAPE) protect the heart?

During restoration of blood flow of the ischemic heart induced by coronary occlusion, free radicals cause lipid peroxidation with myocardial injury. Lipid peroxidation end-products, such as malondialdehyde (MDA), have been used to assess oxygen free radical-mediated injury of the ischemic-reperfused (I/R) myocardium in rats. This experimental study assessed the preventive effect of caffeic acid phenthyl ester (CAPE), antioxidant, on I/R-induced lipid peroxidation in the rat heart. We are also interested in the role of CAPE on glutathione (GSH) levels, an antioxidant whose levels are influenced by oxidative stress. I/R leads to the depletion of GSH which is the major intracellular nonprotein sulphydryl and plays an important role in the maintenance of cellular proteins and lipid in their functional state and acts primarily to protect these important structures against the threat of oxidation. In addition, we also examined morphologic changes in the heart by using light microscopy. The left coronary artery was occluded for 30 min and then reperfused for 120 min more before the experiment was terminated. CAPE (50 μM kg−1) was administered 10 min prior to ischemia and during occlusion by infusion. At the end of the reperfusion period, rats were sacrificed, and the heart was quickly removed for biochemical determination and histopathological analysis. I/R was accompanied by a significant increase in MDA production and decrease in GSH content in the rat heart. Administration of CAPE reduced MDA production and prevented depletion of GSH content. These beneficial changes in these biochemical parameters were also associated with parallel changes in histopathological appearance. These findings imply that I/R plays a causal role in heart injury due to overproduction of oxygen radicals or insufficient antioxidant and CAPE exert cardioprotective effects probably by the radical scavenging and antioxidant activities.

Antiapoptotic and antioxidant effects of β-carotene against methotrexate-induced testicular injury

OBJECTIVE To investigate the effect of beta-carotene against testicular injury induced by methotrexate (MTX). DESIGN Experimental study. SETTING Animal and histology laboratory at Inonu University. ANIMAL(S) Twenty-eight Wistar male rats. INTERVENTION(S) Twenty-eight rats were separated into four groups: control, beta-carotene, MTX, and beta-carotene + MTX. At the end of the treatment, the animals were killed, and tissue samples were examined via histologic and biochemical methods. MAIN OUTCOME MEASURE(S) In each group, 100 tubules were classified as intact, sloughing, atrophic, and degenerated. Caspase-3, a universal effector of apoptosis, was evaluated according to staining in place of coloring as weak, mild, and strong. RESULT(S) In the MTX group, 58.5 + 3.7% of tubules were sloughing, 10.8 + 2.1% of tubules were atrophic, and 2.0 + 0.6% of tubules were degenerative. In the beta-carotene + MTX group, the affected tubule number was statistically significantly lower than in the MTX group. The distribution of caspase-3 in the MTX group showed a statistically significant increase, but it decreased in the beta-carotene + MTX group. The enzyme activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GP-x) and the level of malondialdehyde (MDA) increased and decreased in parallel. CONCLUSION(S) Our results indicate that beta-carotene may be useful in decreasing the side effects of chemotherapy, including apoptotic cell death.

Protective Effect of Β-Carotene on Methotrexate-Induced Oxidative Liver Damage

In this study, the authors aimed to investigate the role of oxidative stress on the hepatic damage caused by methotrexate (MTX) and the possible protective effects of β-carotene against this damage. The rats were divided into four groups as control, MTX (20 mg/kg ip), β-carotene (10 mg/kg/day ip) + MTX, and β-carotene. Histopathologic alterations were evaluated for defining the liver damage. The tissue, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GP-x) contents and serum aspartate aminotransferase (AST) and alanine aminotranferase (ALT) activities were also examined. Histopathologic damage for each group score findings have been determined as control: 0.66 ± 0.33; MTX: 7.0 ± 0.68; β-carotene + MTX: 3.3 ± 0.42; and β-carotene: 0.5 ± 0.3. In the MTX-treated group, MDA, AST, and ALT values were increased, while SOD and GP-x values were decreased compared with the control group. In the β-carotene + MTX-treated group, AST and ALT values significantly decreased, while all other parameters were similar to the control group. This study shows that β-carotene has a protective effect on MTX-induced oxidative hepatic damage. Consequently, it seems that an antioxidant agents like β-carotene may be useful in decreasing the side effects of chemotherapy.

Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats.

The role of oxygen radicals are known for the pathogenesis of kidney damage. The aim of the present study was to investigate the antioxidative effects of melatonin, quercetin, and resveratrol on streptozotocin (STZ)-induced diabetic nephropathy in rats. A total of 35 male Wistar rats were divided into 5 groups as follows: control, diabetes mellitus (DM), DM + melatonin, DM + quercetin, and DM + resveratrol. All the injections started on the same day of single-dose STZ injection and continued for 30 days. At the end of this period, kidneys were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased, whereas body weights were decreased compared with the control group. Significant increases in blood urea nitrogen and tissue malondialdehyde (MDA) levels and decreases in superoxide dismutase and catalase activities were detected in DM group. Administration of melatonin, quercetin, and resveratrol significantly reduced these values. Melatonin was more efficient in reducing MDA levels than other antioxidants (p < 0.05). STZ-induced histopathological alterations including epithelial desquamation, swelling, intracytoplasmic vacuolization, brush border loss and peritubular infiltration. Additionally, basement membrane thickening and sclerotic changes were observed in glomerulus. Transforming growth factor-β1 positive cells were also increased. Melatonin, quercetin, and resveratrol significantly reduced these histopathological changes. Our results indicate that melatonin, quercetin, and resveratrol might be helpful in reducing diabetes-induced renal damage

Protective effect of apricot (Prunus armeniaca L.) on hepatic steatosis and damage induced by carbon tetrachloride in Wistar rats.

The present study was planned to investigate the protective effect of 10 % and 20 % apricot-containing feed on carbon tetrachloride (CCl4)-induced hepatic steatosis and damage. Adult male Wistar rats (n 42) were divided into six groups of seven each, as follows: control group; CCl4 group; CCl4+10 % apricot group; CCl4+20 % apricot group; 10 % apricot group; 20 % apricot group. All apricot groups were fed with 10 % or 20 % apricot-containing feed for 5 months. CCl4 injections were applied to the CCl4 groups at the dose of 1 mg/kg for 3 d at the end of 5 months. In the CCl4 group, vacuolated hepatocytes and hepatic necrosis were seen, especially in the centrilobular area. Hepatocytes showed an oedematous cytoplasmic matrix, large lipid globules and degenerated organelles. The area of liver injury was found significantly decreased with apricot feeding. Malondialdehyde and total glutathione levels and catalase, superoxide dismutase and glutathione peroxidase activities were significantly changed in the CCl4 group and indicated increased oxidative stress. Apricot feeding decreased this oxidative stress and ameliorated histological damage. We concluded that apricot feeding had beneficial effects on CCl4-induced liver steatosis and damage probably due to its antioxidant nutrient (beta-carotene and vitamin) contents and high radical-scavenging capacity. Dietary intake of apricot can reduce the risk of liver steatosis and damage caused by free radicals.

Beneficial effects of montelukast against methotrexate-induced liver toxicity: a biochemical and histological study.

The effects of montelukast against methotrexate-induced liver damage were investigated. 35 Wistar albino female rats were divided into 5 groups as follows: group I: control; group II: montelukast (ML); group III: methotrexate (Mtx); group IV: montelukast treatment after methotrexate application (Mtx + ML); group V: montelukast treatment before methotrexate application (ML + Mtx). At the end of the experiment, the liver tissues of rats were removed. Malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione levels were determined from liver tissues. In addition, the liver tissues were examined histologically. MDA and MPO levels of Mtx group were significantly increased when compared to control group. In Mtx + ML group, these parameters were decreased as compared to Mtx group. Mtx injection exhibited major histological alterations such as eosinophilic staining and swelling of hepatocytes. The glycogen storage in hepatocytes was observed as decreased by periodic acid schiff staining in Mtx group as compared to controls. ML treatment did not completely ameliorate the lesions and milder degenerative alterations as loss of the glycogen content was still present. It was showed that montelukast treatment after methotrexate application could reduce methotrexate-induced experimental liver damage.