Yilmaz Cigremis

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.

The effect of resveratrol in experimental cataract model formed by sodium selenite.

Purpose: To investigate if resveratrol can prevent sodium selenite-induced experimental cataract model in rats. Methods: Forty-eight Spraque-Dawley rat pups were divided into 3 treatment groups: (1) normal saline–% 5 ethanol injected i.p. on postpatum day 10; (2) Na selenite (30 nmol/g body wt) injected s.c on day 10; (3) Na selenite s.c on day 10 + resveratrol (40 mg/kg) i.p on days 10–13. On day 21, cataract development was graded by slit-lamp examination and photography. Encapsulated lenses and erythrocytes were analyzed for reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation. Lenses were also analyzed for total nitrite (TN). Results: All control lenses in group 1 were clear. In group 2, all rats developed cataracts (grade 3–grade 6), whereas in group 3, only 9 of 16 rats developed cataracts (grade 2–grade 3). The difference of cataract frequency between groups 2 and 3 was statistically significant (p < 0.05). Group 3 lenses and erythrocytes had higher mean GSH and lower mean MDA levels than those in group 2 (p < 0.05). TN was highest in group 3 and lowest in group 1 (p < 0.05). Conclusions: Resveratrol suppressed selenite-induced oxidative stress and cataract formation in rats. This protective effect was supported by higher GSH and lower MDA in lens and erythrocytes. The presence of oxidative stress in selenite cataract development and its prevention by resveratrol support the possibility that high natural consumption of resveratrol in food can help prevent human senile cataract.

Melatonin reduces torsion-detorsion injury in rat ovary: biochemical and histopathologic evaluation

Abstract:  This experimental study was designed to determine the effects of melatonin on the levels of malondialdehyde (MDA), reduced glutathione (GSH), xanthine oxidase (XO) after adnexial torsion/detorsion (ischemia/reperfusion, I/R) of the ovaries of in rats. Forty adult albino rats were divided into five groups: sham operation, torsion, I/R plus saline, I/R plus melatonin and torsion plus melatonin. Rats in the sham‐operated group underwent a surgical procedure similar to the other groups but the adnexa was not occluded. Rats in the torsion group were killed after adnexal torsion for 3 hr. Melatonin and saline were injected intraperitoneally (10 mg/kg) 30 min before detorsion to the I/R plus melatonin group and I/R plus saline group respectively. After 3 hr of ovarian detorsion, the rats were killed and ovaries were removed. Melatonin was injected intraperitoneally (10 mg/kg) 30 min before torsion to the torsion plus melatonin group. After 3 hr of ovarian torsion, the rats were killed and ovaries were harvested. The tissue levels of MDA, GSH and XO were measured. MDA and XO levels in the I/R plus saline group increased significantly when compared with torsion and sham‐operated groups (P < 0.001). MDA and XO levels in the I/R plus melatonin group were lower than I/R plus saline and differences between the two groups were statistically significant (P < 0.001). GSH levels in the I/R plus saline group decreased significantly when compared with ischemia and sham‐operated groups (P < 0.001). GSH levels in the I/R plus melatonin treated rats were significantly higher than I/R plus saline and ischemia groups (P < 0.001). The tissue levels of XO, MDA and GSH were similar between ischemia and ischemia plus melatonin groups. Morphologically, polymorphonuclear neutrophil infiltration and vascular dilatation were obvious in the I/R‐damaged ovaries, and the changes also partially reversed by melatonin. This study demonstrates that melatonin protects the ovaries against oxidative damage associated with reperfusion following an ischemic insult.

Resveratrol, a Red Wine Constituent Polyphenol, Protects from Ischemia-Reperfusion Damage of the Ovaries

Objective: The aim of this study is to investigate the effects of resveratrol on histopathological changes, antioxidant status and lipid peroxidation, in torsion-detorsion injury in rat ovaries. Method: To determine whether ischemia followed by reperfusion can induce ovarian oxidative damage, we created a model of adnexal ischemia-reperfusion by using rats. Ischemia was induced by unilateral occlusion of the tubo-ovarian vessels for 3 h. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 3 h. Thirty-two adult female albino rats were divided equally into 4 groups: sham operation, torsion, saline/detorsion and resveratrol/detorsion. Rats in the torsion group were killed after 360° clockwise adnexal torsion for 3 h. Resveratrol was injected intraperitoneally 30 min before detorsion in the resveratrol/detorsion group, and saline was administered in the saline/detorsion group. After 3 h of adnexal detorsion in both of these groups, the rats were killed and adnexa were removed. The tissue levels of malondialdehyde, reduced glutathione and xanthine oxidase activity were measured. Results: Malondialdehyde and xanthine oxidase levels in the saline/detorsion group were increased significantly when compared to the torsion and sham operation groups (p < 0.001). Malondialdehyde levels in the resveratrol group were lower than in the saline/detorsion group, and differences between the two groups were statistically significant (p < 0.001). Xanthine oxidase levels in the resveratrol group were lower than in the saline/detorsion and torsion groups, and differences between these groups were statistically significant (p < 0.001). Reduced glutathione levels in the saline/detorsion group were decreased significantly when compared to the torsion and sham operation groups. Reduced glutathione levels in the resveratrol group were significantly higher than in the saline/detorsion group (p < 0.006). Histological examination showed a significant improvement in ovarian morphology in the resveratrol-treated rats compared with the ischemia and ischemia-reperfusion groups. Conclusion: Our results demonstrated that intraperitoneal resveratrol administration reduced the lipid peroxidation products of ischemic rats and ovarian damage was reduced as indicated by histological examination.

Myocardial ischemia/reperfusion-induced oxidative renal damage in rats: protection by caffeic acid phenethyl ester (CAPE).

Myocardial ischemia-reperfusion (MI/R) may induce renal damage. A rat model of M/IR injury was established. The left coronary artery was clamped for 30 min, constituting the ischemic period, and was then released for 120 min, thus constituting the reperfusion period. The purpose of this study was to evaluate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on renal dysfunction in rats undergoing MI/R. CAPE (50 μmol/kg) was administered by infusion 10 min before ischemia and during occlusion. Hemodynamic changes were recorded during the different periods. At the end of the reperfusion period, rats were sacrificed, and the kidneys were quickly removed for biochemical determination and histopathological analysis. MI/R was accompanied by a significant increase in malondialdehyde (MDA) production and decrease in glutathione (GSH) content in the rat kidney. 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 MI/R plays a causal role in kidney injury through overproduction of oxygen radicals or insufficient antioxidant, and CAPE exerts renal-protective effects probably by its radical scavenging and antioxidant activities.

Caffeic acid phenethyl ester (CAPE) attenuates cerebral vasospasm after experimental subarachnoidal haemorrhage by increasing brain nitric oxide levels

Cerebral vasospasm, a medical complication of aneurysmal subarachnoid hemorrhage (SAH), is associated with high morbidity and mortality rates, even after the aneurysm has been secured surgically or endovascularly. Evidence accumulated during the last decade suggest that scavenging a vasodilator, nitric oxide (NO), by superoxide anions (O2−), and activating a strong vasoconstructor, protein kinase C (PKC), are the two most important mechanisms in the pathogenesis of vasospasm. Our aim in this study was to determine whether caffeic acid phenethyl ester (CAPE), a non‐toxic oxygen free radical scavenger, prevents vasospasm in an experimental rat model of SAH.

Caffeic acid phenethyl ester prevents ovary ischemia/reperfusion injury in rabbits.

Protective effect of caffeic acid phenethyl ester (CAPE) on ovary ischemia/reperfusion (IR) injury was investigated in this study. Twenty four New Zealand rabbits were divided into 4 groups as follows: group S served as sham. Group C was intraperitoneally injected with CAPE (8.5mg/kg). In groups E+IR and C+IR, 1% ethanol and CAPE was given intraperitoneally before torsion, respectively. Then, the ovaries were subjected to IR in both groups. Ovary reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in group E+IR were significantly reduced compared to that of group S. GSH level and GSH-Px activity was significantly increased in group C+I/R. Thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity in group E+I/R was significantly higher than in group S. CAT activity was decreased to normal levels by CAPE treatment in group C+I/R, while TBARS in group C+IR was significantly reduced compared to that of E+IR. According to histopathological examination, severe congestion, hemorrhage, edema and leukocyte infiltration were observed in E+I/R group. CAPE prominently reduced degenerative effects of IR injury thus it alleviates free radical damage. In conclusion, CAPE which is able to prevent IR-induced injury in the ovaries may be of therapeutic value before the surgical correction.

Resveratrol ameliorates cisplatin-induced oxidative injury in New Zealand rabbits

This study investigated the preventive role of resveratrol in cisplatin-induced nephrotoxicity. The study used groups of New Zealand rabbits that were treated as follows: group C (cisplatin treated), group R (resveratrol treated), group R+C (resveratrol + cisplatin treatment), and group E (control group). Kidney levels of glutathione were significantly lower in group C than in groups E and R, whereas glutathione levels in group R+C were found to be similar to the control values. Malondialdehyde levels in group C were significantly higher than in groups E and R. However, malondialdehyde levels in group R+C were similar to group E. Kidney levels of nitric oxide were significantly higher in the cisplatin group than in the control, whereas nitric oxide levels were at basal values in group R+C. Cisplatin treatment significantly reduced kidney levels of glutathione peroxidase, superoxide dismutase, and catalase activity compared with those of group E, whereas resveratrol treatment significantly increased levels of glutathione peroxidase, superoxide dismutase, and catalase activity in group R+C. However, cisplatin injection did not affect mRNA levels of glutathione peroxidase, superoxide dismutase, or catalase enzymes. Histopathological and immunohistochemical analyses indicated that cisplatin caused kidney damage, which was mostly prevented by resveratrol treatment. In conclusion, resveratrol ameliorates cisplatin-induced oxidative injury in the kidney of rabbit.

The effects of intracerebroventricular infusion of irisin on feeding behaviour in rats

Irisin, a novel exercise-induced myokine, has attracted attention with its effects on energy metabolism. This study was conducted to determine the possible effects of irisin on nutritional behaviour. In this study, 40 male Wistar Albino rats were separated into 4 groups (n=10 for each group). Osmotic mini-pumps were connected to metal cannulas implanted to lateral ventricle; and artificial cerebrospinal fluid (vehicle), and 10 and 100nM of irisin was infused for 7days. The daily food and water consumptions and body weights of rats were followed up. After the infusion, the animals were killed, and the hypothalamus and blood samples were collected. NPY, POMC, and UCP2 mRNA levels in the hypothalamus were examined by RT-PCR. In serum, leptin and ghrelin levels as well as the levels of metabolic parameters were measured by using ELISA. It was determined that irisin administration increased the daily food consumption (p<0.05), without causing significant changes in water consumption and body weight. Irisin also caused increases in ghrelin level in circulation and NPY and UCP2 mRNA levels in the hypothalamus, whereas it decreased the leptin level in circulation and POMC mRNA levels in the hypothalamus (p<0.05). Otherwise, irisin caused decrease in LDL, triglycerides and cholesterol levels, while increasing HDL and glucose levels (p<0.05). Results indicates that long-term irisin treatment increases food intake without increasing body weight associated with increased ghrelin, NPY and UCP2 mRNAs, and decreased leptin and POMC mRNA in the hypothalamus.

The effect of apricots on the experimental cataract model formed by sodium selenite.

This study was designed in order to investigate whether sun dried apricots have a preventive effect on the experimental cataract model formed by sodium selenite in rats. Fifty-nine Spraque-Dawley rat pups were divided into three groups. Group 1 (control group) consisted of twenty rat pups, born from the rats nourished ad libitum. Group 2 consisted of 18 newborn rats, born from the rats nourished ad libitum with 10% sun dried natural apricots. Group 3 consisted of 21 newborn rats, born from the rats nourished ad libitum. Subcutaneous (30nmol/gr) sodium selenite injection was applied to all the newborn rats except the control group (Group 1) on postpartum day 10. Cataract development was graded by slit-lamp examination and photography. Encapsulated lenses were analyzed for reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid per oxidation. Lenses were also analyzed for total nitrite (TN). The presence of oxidative stress in selenite cataract development and its prevention by sun dried apricots.