Protective Effects of Quercetin on Oxidative Stress-Induced Tubular Epithelial Damage in the Experimental Rat Hyperoxaluria Model.

Background and Objectives: The most common kidney stones are calcium stones and calcium oxalate (CaOx) stones are the most common type of calcium stones. Hyperoxaluria is an essential risk factor for the formation of these stones. Quercetin is a polyphenol with antioxidant, anti-inflammatory, and many other physiological effects. The aim of this study was to investigate the protective effect of quercetin in hyperoxaluria-induced nephrolithiasis. Materials and Methods: Male Wistar-Albino rats weighing 250-300 g (n = 24) were randomized into three groups: Control (n = 8), ethylene glycol (EG) (n = 8), and EG + quercetin (n = 8). One percent EG-water solution was given to all rats except for the control group as drinking water for five weeks. Quercetin-water solution was given to the EG + quercetin group by oral gavage at a dose of 10 mg/kg/day. Malondialdehyde (MDA), catalase (CAT), urea, calcium, and oxalate levels were analyzed in blood and urine samples. Histopathological assessments and immunohistochemical analyses for oxidative stress and inflammation indicators p38 mitogen-activated protein kinase (p38-MAPK) and nuclear factor kappa B (NF-kB) were performed on renal tissues. Results: The MDA levels were significantly lower in the quercetin-treated group than in the EG-treated group (p = 0.001). Although CAT levels were higher in the quercetin-treated group than the EG-administered group, they were not significantly different between these groups. The expression of p38 MAPK was significantly less in the quercetin-treated group than the EG group (p < 0.004). There was no statistically significant difference between the quercetin and EG groups in terms of NF-kB expression. Conclusions: We conclude that hyperoxaluria activated the signaling pathways, which facilitate the oxidative processes leading to oxalate stone formation in the kidneys. Our findings indicated that quercetin reduced damage due to hyperoxaluria. These results imply that quercetin can be considered a therapeutic agent for decreasing oxalate stone formation, especially in patients with recurrent stones due to hyperoxaluria.

Evaluation of the effects of vitamins C and E on experimental orthodontic tooth movement.

Background. This experimental study aimed to assess the effects of Vitamins C and E on orthodontic tooth movement. Methods. Fifty-one male Wistar albino rats were divided into six groups: five appliance groups and one control group. The appliance groups had an orthodontic appliance consisting of a closed-coil spring ligated between the maxillary incisor and maxillary first molar (50 g). Vitamin E and C (150 mg/kg) were injected intraperitoneally per day in the first and second groups, respectively. Vitamins E and C (20 µL) were locally injected into the periodontal gap of the moving teeth in the third and fourth groups, respectively, once every three days. No vitamin was injected in the last (fifth) appliance group.The experimental period was 18 days. Histological and biochemical (alkaline phosphatase, osteocalcin, and NTx levels) evaluations of the samples were performed, and maxillary incisor‒molar distance was measured before and after the experiment. Results. The amount of tooth movement was similar in the appliance groups. All the vitamin groups showed significantly increased osteoblastic activity, while those treated with systemic vitamins exhibited significantly increased numbers of collagen fibers on the tension side compared to the appliance control group (P<0.05). Conclusion. Vitamin C and E supplements positively affected bone formation on the tension side of the teeth during experimental orthodontic tooth movement.

Effects of misoprostol on cisplatin-induced renal damage in rats.

Cisplatin (CP) is a potent anticancer drug. However, it has side effects on kidney such as nephrotoxicity. Abnormal production of reactive oxygen species (ROS) has been accused in the etiology of CP-induced nephrotoxicity. Several ROS scavengers have been reported to prevent nephrotoxicity after CP administration. In this study, we used prostaglandin E1 (PGE1) analogues misoprostol (MP) to reduce this damage. MP has gained considerable interest as a ROS scavenger. Rats were received a single injection of CP (5 mg/kg, i.p.) with or without MP pretreatment (200 mcg/kg, orally). The renal tissue morphology was investigated by light microscopy. Trunk blood was also obtained to determine lipid peroxidation product malondialdehyde (MDA) and activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT). CP administration increased MDA production and decreased SOD and CAT levels in the kidney tissue when compared to the control group. Morphological damage in CP administrated rats was also severe in the kidney tissue. MP treatment after CP application protected the renal tissues from CP's side effect. These findings indicate that MP has beneficial effects on CP induced nephrotoxicity in rats.

Effects of aspirin and nimesulide on tissue damage in diabetic rats.

This study was designed to compare the effect of Aspirin (AS) and Nimesulide (NM) on renal failure and vascular disorder in streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups; control, diabetic rats, diabetic rats plus AS and diabetic rats plus NM, which are COX inhibitors. The renal and aorta tissues morphology were investigated by light microscopy. Trunk blood was also obtained to determine plasma lipid peroxidation product malondialdehyde (MDA) and plasma activity of antioxidant enzymes. MDA levels were increased in the diabetic rats when compared to the control group. AS and NM administration caused a significant decrease in MDA production. Morphological damage in diabetic rats was severe in the kidney and in the aorta tissue. Treatment of AS reduced these damages, but NM did not exert positive effect on these damages in diabetic rats. As a result, although both AS and NM corrected lipid peroxidation parameters such as MDA via their antioxidant properties, only AS ameliorated pathological alteration in tissues. These findings indicate that there may be another mechanism in beneficial effect of AS in diabetic rats.

Effects of pentoxifylline on amikacin-induced nephrotoxicity in rats.

The nephrotoxicity of amikacin (AK) was prevented with pentoxifylline (PTX) in a rat model. Rats were received a single injection of AK (1.2 g/kg, i.p.) with or without PTX pretreatment (25 mg/kg, orally). Renal morphology was investigated by light microscopy. Tissue samples and trunk blood were also obtained to determine renal malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine (Cr) levels. MDA production was found to be higher in AK group. PTX administration caused a significant decrease in MDA production. Morphological damage in rats given AK was severe in the kidney, whereas in rats given AK plus PTX, no histological changes occurred. It is concluded that PTX could be useful for reducing the nephrotoxic effects of AK.

Effect of long-term fluoride exposure on lipid peroxidation and histology of testes in first- and second-generation rats.

This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls and fluoride-given group, each of which containing five rats. Pregnant rats in the fluoride-given group were exposed to a total dose of 30 mg/l sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/l of NaF throughout the gestation and lactation periods. After the lactation period, the young animals (first generation, F1) were exposed to the same dose of NaF in drinking water for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F1) were killed and testes tissues were taken for histopathological and biochemical analysis. The remaining eight female rats were mated with four males (2:1) for approximately 12 h to obtain second-generation rats. Six female were identified as pregnant and treated with similarly throughout the gestation and the lactation periods. After the lactation period, the young male animals (second generation, F2) were also treated in the same way for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F2) were killed and testes tissues were collected for histopathological and biochemical analysis. The rats in the control group were applied the same procedure without NaF administration. In biochemical analysis of the fluoride given F1 and F2 rats, it has been found that plasma fluoride levels and testes thiobarbituric acid reactive substance levels were significantly increased when compared with the control group. In F1 and F2 rats, similar histopathological changes were observed. In both groups, spermatogenesis was severely reduced. Spermatogonia and primary spermatocytes were normal, however, there was a widespread degeneration in other spermatogenic cell lines of the seminiferous epithelium. The histological structures of the Sertoli and interstitial Leydig cells were normally observed. It is concluded that chronic fluorosis exposure leads to a remarkable destruction in testes tissues of F1 and F2 rats via lipid peroxidation.

Effect of chronic fluorosis on lipid peroxidation and histology of lung tissues in first and second generation rats.

This experiment was designed to investigate the lipid peroxidation and histological effects of chronic fluorosis on first and second generation rat lung tissues. Sixteen, virgin, female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two experimental groups (control and fluoride supplemented). The pregnant rats in the fluoride-supplemented group were exposed to 30 mg/L sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/L NaF throughout the gestation and lactation periods. After the lactation period, young animals (first generation; F1) were exposed to the same amount of NaF in drinking water for four months. At the end of the four-month experimental period, nine randomly-chosen male rats (F1) were sacrificed and lung tissues were removed for histopathological and enzymatic lipid peroxidation examination. The second generation rats were obtained from the remaining rats by the same method. They were also treated similarly. At the end of the four-month experimental period, nine randomly-chosen male rats (F2) were sacrificed, and the lungs were removed for histological and lipid peroxidation examination. The rats in the control groups underwent the same procedure without NaF supplementation. It was found that the plasma fluoride and the lung TBARS levels of fluoride supplemented F1 and F2 rats were higher than controls. There were marked histological changes in the lung tissues of fluoride supplemented F1 and F2 rats, as follows: in F1 rats; loss of alveolar architecture, emphysematous areas, descuamation of alveolar epithelium and alveolar congestion were observed. There were thickened interalveolar septae and congestion of alveolar septal vessels. Intraparenchymal thick-walled vessels were also observed. There were markedly perivascular and intraparenchymal focal mononuclear cell infiltrations. In F2 rats, in addition to these changes, there were lipid cell hyperplasia and increased connective tissue mass in the parenchymal areas. It is concluded that chronic fluorosis causes a marked destruction in lung tissues of F1 and F2 rats by causing lipid peroxidation.

Effect of chronic fluorosis on lipid peroxidation and histology of kidney tissues in first- and second-generation rats.

This experiment was designed to investigate the lipid peroxidation and histological effects of chronic fluorosis on first- and second-generation rat kidney tissues. Sixteen virgin female Wistar rats were mated with eight males (2: 1) for approx 12 h to obtain first-generation rats. Mating was confirmed by the presence of sperm in vaginal smears. Sperm in vaginal smears was observed in 10 of 16 rats (d 0). These rats were identified as pregnant and included in this experiment. Pregnant rats were divided into two experimental groups (control and fluoride-supplemented), each containing five rats. The pregnant rats in the fluoride-supplemented group were exposed to 30 mg/L sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/L NaF throughout the gestation and the lactation periods. After the lactation period, young animals (first generation [F1]) were exposed to the same amount of NaF in drinking water for 4 mo. At the end of the 4-mo experimental period, nine randomly chosen male rats (F1) were sacrificed, and the kidneys were removed for the histological and lipid peroxidation examinations. The remaining eight female rats were mated with four males (2: 1) for approx 12 h to obtain second-generation rats. Six female were identified as pregnant, and treated similarly throughout the gestation and the lactation periods. After the lactation period, the young male rats (second-generation male rats [F2]) were also treated similarly for 4 mo. At the end of the 4-mo experimental period, nine randomly chosen male rats (F2) were sacrificed, and the kidneys were removed for the histological and lipid peroxidation examinations. The rats in the control groups underwent the same procedure without NaF supplementation. It was found that the plasma fluoride and kidney TBARS levels of fluoride-supplemented F1 and F2 rats were higher than controls. Hydropic epithelial cell degenerations and moderate tubular dilatation were observed in some proximal and distal tubules. There were markedly focal mononuclear cell infiltrations and hemorrhage at some areas of the interstitium, especially at the corticomedullar junction. Mononuclear cell infiltrations were also evident in some peritubular and perivascular areas. Most of the vascular structures were congestive. Many Bowman capsules were narrowed. The severe degenerative changes in most of the shrunken glomerules and vascular congestion were also observed.

Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats.

OBJECTIVES: To justify the effects of Mentha piperita labiatae and Mentha spicata labiatae herbal teas on plasma total testosterone, luteinizing hormone, and follicle-stimulating hormone levels and testicular histologic features. We performed this study because of major complaints in our area from men about the adverse effects of these herbs on male reproductive function. METHODS: The experimental study included 48 male Wistar albino rats (body weight 200 to 250 g). The rats were randomized into four groups of 12 rats each. The control group was given commercial drinking water, and the experimental groups were given 20 g/L M. piperita tea, 20 g/L M. spicata tea, or 40 g/L M. spicata tea. RESULTS: The follicle-stimulating hormone and luteinizing hormone levels had increased and total testosterone levels had decreased in the experimental groups compared with the control group; the differences were statistically significant. Also, the Johnsen testicular biopsy scores were significantly different statistically between the experimental groups and the control group. Although the mean seminiferous tubular diameter of the experimental groups was relatively greater than in the control group, the difference was not statistically significant. The only effects of M. piperita on testicular tissue was segmental maturation arrest in the seminiferous tubules; however, the effects of M. spicata extended from maturation arrest to diffuse germ cell aplasia in relation to the dose. CONCLUSIONS: Despite the beneficial effects of M. piperita and M. spicata in digestion, we should also be aware of the toxic effects when the herbs are not used in the recommended fashion or at the recommended dose.

Investigation on the histopathological effects of thyroidectomy on the seminiferous tubules of immature and adult rats.

INTRODUCTION: This study aimed to investigate the histopathological effects of thyroidectomy on both immature and adult rat testes. MATERIALS AND METHODS: Male albino Wistar rats, 4 weeks old and weighing between 45 and 55 g, were used for this study. The experimental groups were as follows: 2-week control group (group I); 2-week thyroidectomy group (group II); 4-week control group (group III); 4-week thyroidectomy group (group IV); 6-week control group (group V), and 6-week thyroidectomy group (group VI). The control groups included both sham-operated and untreated rats. In groups II, IV and VI, total thyroidectomy was performed under ether anesthesia in all rats at 4 weeks of age. The rats were killed in the 2nd, 4th and 6th weeks, respectively, following the thyroidectomy. The testes of each animal were evaluated histologically. RESULTS: In group II, spermatogenesis progressed to meiosis but round spermatids were found to be decreased and pachytene spermatocytes were observed to be increased when compared to group I. Giant pachytene spermatocytes were seen. There were also many degenerated cells of intermediate origin in the seminiferous epithelium. In groups IV and VI, spermatogonia and primary spermatocytes were normal in appearance, but there was widespread degeneration of the other spermatogenic cells. In addition, some closed lumina covered by degenerated and dead cells were observed. In group II, the mean outer diameter, luminal diameter and area occupied by seminiferous epithelium decreased by 19.74, 32.18, and 28.12%, respectively. In group IV, these data decreased by 23.9, 16.52, and 48.5%, respectively, and in group VI, by 21.10, 19.76 and 40.29%, respectively, when compared with the control groups. These data were statistically significant (p < 0.001). CONCLUSIONS: Thyroid hormones could have a marked influence on the seminiferous tubules of both immature and adult rats, and their permanent lack results in a depression in seminiferous tubule growth as shown by the reduced outer and luminal diameters and area occupied by the seminiferous epithelium, which could give rise to degenerative changes in the spermatogenic cells of thyroidectomized rats. In addition, all these changes could also result from both the inability of Sertoli cells to support spermatogenic cells and the diminished levels of GH and FSH.

Investigation of biochemical and histopathological effects of Mentha piperita L. and Mentha spicata L. on kidney tissue in rats.

Peppermint plants have been used as a herbal medicine for many conditions, including loss of appetite, common cold, bronchitis, sinusitis, fever, nausea, vomiting and indigestion. This study is aimed at investigating the biochemical and histological effects of Mentha piperita L., growing in the Yenisar Bademli town of Isparta City, and Mentha spicata L., growing on the Anamas high plateau of Isparta City, on rat kidney tissue. Forty-eight male Wistar albino rats weighing 200-250 g were used for this study. Animals were divided into four experimental groups, each with 12 rats, as follows: control group (group I); 20 g/L M. piperita tea (group II); 20 g/L M. spicata tea (group III); 40 g/L M. spicata tea (group IV). The control group rats were given commercial drinking water (Hayat DANONESA water). The tea for the other groups was prepared daily and provided at all times to the rats during 30 days as drinking water. Plasma urea and creatinine levels were determined, and the levels of thiobarbituric acid reactive substance (TBARS) and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. The levels of plasma urea and creatinine were increased significantly (P < 0.0033) in groups III and IV when compared with group I. The activities of SOD and GSH-Px were decreased significantly (P < 0.0033) in group IV when compared with group I. The activities of CAT were decreased significantly in groups III and IV (P < 0.033, P < 0.0033, respectively) when compared with group I. TBARS levels were increased significantly (P < 0.0033) in groups III and IV when compared with group I. In groups II, III and IV, hydropic degeneration of tubular epithelial cells, the epithelial cells with picnotic nuclei and eosinophilic cytoplasm, tubular dilatation and enlargements in Bowman capsules were observed histologically. However, in group II histopathological changes were more slight than in groups III and IV. In group IV, in addition to these changes, extremely hydropic degeneration of tubular epithelial cells, some atrophic tubules and glomerules, and focal mononuclear cell infiltrations in the kidney tissues of the rats were observed. In conclusion, the results indicate that M. piperita does not show nephrotoxicity but M. spicata presents markedly nephrotoxic changes in rats.

Protective role of melatonin and a combination of vitamin C and vitamin E on lung toxicity induced by chlorpyrifos-ethyl in rats.

The ameliorating effects of melatonin and vitamin C plus vitamin E were examined histologically and biochemically in lung tissues in rats exposed to chlorpyriphos-ethyl (CE). Experimental groups were as follows: Control group (C), CE treated group (CE), vitamin C plus vitamin E treated group (Vit), melatonin treated group (Mel), vitamin C plus vitamin E plus CE treated group (Vit + CE), and melatonin plus CE treated group (Mel + CE). Vitamin E and vitamin C were administered intramuscularly at the rates of 150 and 200 mg per kg body weight, respectively, in Vit and Vit + CE groups, once a day for 6 consecutive days. Melatonin was administered intramuscularly at the rate of 10 mg per kg body weight in Mel and Mel + CE groups, once a day for 6 consecutive days. At the end of the fifth day, the rats of CE, Vit + CE and Mel + CE groups were treated orally with CE dissolved in corn oil with two equal doses of 41 mg CE per kg body weight at zero and twenty-first hours. Tissue samples of lungs were taken by using appropriate techniques for biochemical and histological examinations under anesthesia at the twenty-fourth hours of CE administration, at the end of the sixth day of the experiment. In tissue homogenates, the level of thiobarbituric acid reactive substances (TBARS), antioxidant potential (AOP), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined. TBARS was significantly high (p < 0.05) in CE group compared to control group, while TBARS was found to significantly decrease (p < 0.05) with Vit and Mel groups compared to control. On the other hand, TBARS was seen to significantly decrease (p < 0.05) in both groups of Vit + CE and Mel + CE compared to CE group. In comparison with CE group, SOD activity was significantly high (p < 0.05) with the groups of Vit, Mel, Vit + CE and Mel + CE. GSH-Px activity was found to significantly decrease (p < 0.05) with CE group, compared with both C and Vit groups. AOP was significantly lower (p < 0.01) in CE group than C group. Although there was an increased AOP with Vit + CE and Mel + CE groups compared to CE group, the increase in AOP was only seen to be significant (p < 0.05) in Mel + CE group. In comparison with C group, AOP significantly (p < 0.05) increased with Vit group. There was also a significant (p < 0.05) increase in AOP with Mel + CE group, compared with CE group. Additionally, AOP was significantly lower (p < 0.05) in Vit + CE group than Mel + CE group. Lungs were examined histologically at the end of sixth day. There were remarkable changes in the histomorphology of peribronchial and perivascular area in the lung of rats treated with CE. These were infiltration of mononuclear cells (such as lymphocytes, plasmocytes, macrophages), hyperplasia of type II pneumocyte, and thickened and increased connective tissue. Damage to the lung tissue such as increased inflammatory mononuclear cells in peribronchial and perivascular areas were more pronounced for the CE group than Vit + CE and Mel + CE groups in which these changes were higher than C, Vit and Mel groups. These results suggest that CE increases lipid peroxidation and decreases antioxidant enzymes activities and AOP due to increasing oxidative stress induced by CE, and high doses of vitamin C plus vitamin E and melatonin considerably reduce CE toxicity in lung tissues of rats.