Ali Otlu

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.

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 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.

The protective effects of Prunus armeniaca L (apricot) against methotrexate-induced oxidative damage and apoptosis in rat kidney

This study was conducted to evaluate a possible protective role of apricot in apoptotic cell death induced by methotrexate (MTX) and renal damage by different histological and biochemical parameters. Twenty-eight rats were divided into four groups, control, apricot, methotrexate, and apricot + methotrexate. Methotrexate induced renal failure, as shown by significant serum creatinine and urea elevation. Additionally, the results indicated that methotrexate significantly induced lipid peroxidation and reduced antioxidant activities in rats. In contrast, apricot significantly prevented toxic effects of methotrexate via increased catalase, superoxide dismutase, and glutathione levels but decreased formation of malondialdehyde. Also, it was determined that exposure to methotrexate leads to significant histological damage in kidney tissue such as glomerulosclerosis and apoptosis. On the other hand, these effects can be eliminated with apricot diet. These data indicate that apricot may be useful in preventing undesirable effects of MTX such as nephrotoxicity.

Apricot ameliorates alcohol induced testicular damage in rat model.

In this study, we intended to determine the possible preventive effects of dietary apricot on oxidative stress due to ethanol usage in rat testes. The animals were divided into six groups as follows: Group 1 was control. Group 2 received ethanol. Group 3 were fed with apricot diet for 3 months. Group 4 were fed with apricot diet for 6 months. Group 5 received ethanol and apricot diet for 3 months. Group 6 were fed apricot diet for 3 months, and then ethanol+apricot diet for 3 months. Following sacrification, the testes were treated for morphological (tubular and germ cell histology, Sertoli and Leydig cell counts) and biochemical (superoxide dismutase, glutathion peroxidase, catalase, malondialdehyde) analyses. In Group 2, severe histopathological changes in seminiferous tubules and germ cells were determined as well as tubular degeneration and atrophy. Sertoli and Leydig cell counts in the interstitial tissue were decreased. Biochemical parameters revealed tissue oxidative stress. Similar alterations existed in Group 5, although to a lesser extent. In Groups 1, 3 and 4, no histopathological alterations were noted. Results of Group 6 were similar to the controls. Apricot rich diet may have a preventive role on histopathological changes caused by alcohol in rat testes.

Oral L-arginine protects against cyclosporine-induced hepatotoxicity in rats.

Cyclosporine A (CyA) leads to liver injury, probably by causing the production of free radicals and resulting in nitric oxide (NO) deficiency. We evaluated CyA-mediated liver damage histopathologically to determine the possible beneficial effects of L-arginine (L-Arg). In this study, 7 groups of Sprague-Dawley rats; (1) Control group; (2) 0.9% NaCl group; (3) CyA group: 7.5mg/kg/day; (4) L-Arg group: 2g/lt/day; (5) l-NAME (N-nitro-L-arginine methyl ester) group: 5mg/100ml/day; (6) CyA+L-Arg group: L-Arg (2g/lt/day)+CyA (7.5mg/kg/day); and (7) CyA+L-NAME group: CyA (7.5mg/kg/day)+L-NAME (5mg/100ml/day) were included. At the end of the treatments, animals were killed and hepatic tissues were treated for morphological (hematoxylin and eosin) and biochemical (NO and malondialdehyde, MDA) analyses, and serum was processed for biochemical (alanine transaminase (ALT), aspartate transaminase (AST), bilirubin, alkaline phosphatase (ALP) and total protein) study. The results indicated that CyA-induced hepatotoxicity was characterized by sinusoidal dilatation, hepatocellular vacuolization, neutrophilic infiltration and hepatocellular necrosis. These findings were less pronounced in the CyA+L-Arg group than CyA alone group. L-NAME group showed moderate changes. The CyA+L-NAME (Group 7) had more severe changes. We found changes in tissue NO and MDA levels. We think that the tissue damage caused by CyA is mild and reversible at the period when biochemical parameters are just starting to become abnormal and that L-Arg may have a protective effect against CyA damage on liver.

Prunus armeniaca L (apricot) protects rat testes from detrimental effects of low-dose x-rays

Exposure to low x-ray doses damages the spermatozoa, mainly by late-onset (ie, after 3 months) oxidative stress. Antioxidants ameliorate oxidation and prevent tissue damage. Prunus armeniaca L (apricot), rich in carotenoids and vitamins, is a potent natural antioxidant. We hypothesized that an apricot-rich diet might ameliorate the detrimental effects of low-dose x-rays on testis tissue. A 20% apricot diet was composed isoenergetically to the regular rodent diet. The total phenolic content, reducing power, and antioxidant capacity of both diets were determined. Sprague-Dawley rats received apricot-rich diets before and after x-ray exposure. Regular diets were given to controls. Rats were exposed to 0.2 Gy x-rays at the eighth week and were euthanized at the 20th postexposure week. Testicular oxidative status was determined by tissue thiobarbituric acid-reactive substances, reduced glutathione, superoxide dismutase, and catalase activities. For histologic evaluation, qualitative and quantitative microscopic determinations were performed, and Leydig and Sertoli cell counts and Johnsen scores were measured. The control diet group had significant testicular oxidative stress and mild tissue deterioration. Leydig and Sertoli cell counts, tubule diameters, and Johnsen scores were significantly decreased in the exposure groups. Apricot-rich diet significantly ameliorated the oxidative status and prevented the damage in tubular histology. The protective effects were prominent when the diet was maintained throughout the time course and were partially protected when the diet was initiated after exposure. The natural antioxidant activity of apricot ameliorates the delayed detrimental effects of low-dose irradiation on testis tissue. The high total antioxidant capacity of the apricot deserves further investigation.

Protective effect of hesperidin on oxidative and histological liver damage following carbon tetrachloride administration in Wistar rats

Introduction In the current study, the protective effect of hesperidin (HP) on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats was investigated. Material and methods Twenty-eight rats were divided equally into four groups. The first group was kept as a control and given only vehicle. In the second, rats were orally administered 50 mg/kg/day HP for 10 days. Carbon tetrachloride was given in a single intraperitoneal injection at the dose of 2 ml/kg in the third group. In the fourth group, the rats were treated with equal doses of CCl4 and HP. Results It was found that CCl4 induced oxidative stress via a significant increase in the formation of thiobarbituric acid-reactive substances (TBARS) and caused a significant decline in the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in rats. In contrast, HP blocked these toxic effects induced by CCl4, causing an increase in GSH, CAT and SOD levels and decreased formation of TBARS (p < 0.01). In addition, histopathological damage increased with CCl4 treatment. In contrast, HP treatment eliminated the effects of CCl4 and stimulated anti-apoptotic events, as characterized by reduced caspase-3 activation. Conclusions The current study demonstrated that CCl4-induced hepatotoxicity can be prevented with HP treatment. Thus, co-administration of HP with CCl4 may be useful for attenuating the negative effects of CCl4 on the liver.

Histological and Biochemical Effects of Dexmedetomidine on Liver during an Inflammatory Bowel Disease

Abstract Inflammation in the liver is an extraintestinal manifestation that is frequently seen during inflammatory bowel diseases (IBD). The authors investigated histopathologycal, ultrastructural and antioxidant effects of dexmedetomidine (Dex) on liver during trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease. Thirty-two BALB/c mice were divided (n = 8) as follows: control; Dex (dexmedetomidine) (30 μg/kg) for 6 days; TNBS 150 μL, TNBS + ethanol (50% w/v) intrarectally; TNBS + Dex. The histopathological and ultrastructural changes were evaluated. The levels of malondialdehyde (MDA), activity of antioxidant enzymes (GPx and SOD) were measured in liver tissue. Induction of colitis induced histopathological and ultrastructural changes of damage in liver. Those changes were markedly reduced in the TNBS + Dex group and that reduction was even significant in comparison to the TNBS group. MDA levels were significantly higher in the TNBS group and dexmedetomidine significantly elevated SOD levels in the TNBS + Dex group. These results suggest that the administration of dexmedetomidine reduces the histopathological and ultrastructural damage and increases the defense capacity against oxidative damage on liver in this IBD mice model.

Histopathological, Ultrastructural and Apoptotic Changes in Diabetic Rat Placenta

BACKGROUND The exchange of substances between mother and fetus via the placenta plays a vital role during development. A number of developmental disorders in the fetus and placenta are observed during diabetic pregnancies. Diabetes, together with placental apoptosis, can lead to developmental and functional disorders. AIMS Histological, ultrastructural and apoptotic changes were investigated in the placenta of streptozotocin (STZ) induced diabetic rats. STUDY DESIGN Animal experimentation. METHODS In this study, a total of 12 female Wistar Albino rats (control (n=6) and diabetic (n=6)) were used. Rats in the diabetic group, following the administration of a single dose of STZ, showed blood glucose levels higher than 200 mg/dL after 72 hours. When pregnancy was detected after the rats were bred, two pieces of placenta and the fetuses were collected on the 20(th) day of pregnancy by cesarean incision under ketamine/ xylazine anesthesia from in four rats from the control and diabetic groups. Placenta tissues were processed for light microscopy and transmission electron microscopy (TEM). Hematoxylin-eosin (HE) and periodic acid Schiff-diastase (PAS-D) staining for light microscopic and caspase-3 staining for immunohistochemical investigations were performed for each placenta. Electron microscopy was performed on thin sections contrasted with uranyl acetate and lead nitrate. RESULTS Weight gain in the placenta and fetuses of diabetic rats and thinning of the decidual layer, thickening of the hemal membrane, apoptotic bodies, congestion in intervillous spaces, increased PAS-D staining in decidual cells and caspase-3 immunoreactivity were observed in the diabetic group. After the ultrastructural examination, the apoptotic appearance of the nuclei of trophoblastic cells, edema and intracytoplasmic vacuolization, glycogen accumulation, dilation of the endoplasmic reticulum and myelin figures were observed. In addition, capillary basement membrane thickening, capillary endothelial cells chromatin condensation in the nucleus and corrugation of the nucleus were found. CONCLUSION Diabetes causes histomorphometric, ultrastructural and apoptotic changes in rat placenta.