Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

Ameliorative effect of selenium in cisplatin-induced testicular damage in rats.

In this study, we investigated the protective effect of selenium (Se) on cisplatin (Cis) induced testicular damage using histopathological, immunohistochemical and biochemical approaches. Twenty-one male Wistar rats were equally divided into three groups of seven rats each: control (C), Cis, and Cis+Se. Cis and Cis+Se group rats received Cis at a dose of 12mg/kg b.w./day, intraperitoneally for 3 consecutive days. Cis+Se group rats received selenium via oral gavage 3mg/kg/day (twice-a day as 1.5mg/kg) until 11th consecutive days starting at 5 days before cisplatin injection. C group received only 0.9% NaCl intraperitoneally and orally at same time and at equal volume. After the treatment, the histopathological, immunohistochemical and biochemical examinations were performed. In seminiferous tubules of Cis treated rats were observed the most consistent findings characterized with vacuolization, desquamation, disorganization, and also was a considerable reduction in elongated spermatids, however the Cis+Se group exhibited improved histopathologic changes. In the immunohistochemical examinations, caspase-3 immunopositive cells displayed higher in the Cis group according to C and Cis+Se groups. Bcl-2 and NF-κB staining revealed a moderate number in the C group and significantly fewer in the Cis group compared to the Cis+Se groups. Additionally, MDA levels were also significantly increased in the Cis group in comparison to Control group, but pretreatment with selenium prevented elevation of MDA levels significantly in Cis+Se group rats. This study indicates that Cis-treatment induced testicular apoptosis and lipid peroxidation, and combined treatment with selenium prevented severity of the toxicity in rats.

Therapeutic Effects of Melatonin on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical and Immunohistochemical Study.

BACKGROUND: The present study aims to investigate the effects of systemic melatonin administration on alveolar bone resorption in experimental periodontitis in rats. METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups (control, experimental periodontitis [Ped], and experimental periodontitis treated with melatonin [Mel-Ped]). For periodontitis induction, first molars were ligatured submarginally for 4 weeks. After ligature removal, rats in the Mel-Ped group were treated with a daily single dose of 10 mg/kg body weight melatonin for 15 consecutive days. At the end of the study, intracardiac blood samples and mandible tissues were obtained for histologic, biochemical, and radiographic analysis. Serum markers related to bone turnover, calcium, phosphorus, bone alkaline phosphatase (b-ALP), and terminal C telopeptide of collagen Type I (CTX) were analyzed. Myeloperoxidase levels were determined in gingival tissue homogenates, and receptor activator of nuclear factor-kappa B ligand (RANKL) activation was analyzed in the mandible samples stereologically. Alveolar bone loss was also evaluated radiographically in the mandible samples of each group. RESULTS: Melatonin treatment decreased serum CTX levels and increased b-ALP levels. Serum calcium and phosphorus levels were not statistically different among groups (P >0.05). Alveolar bone resorption and myeloperoxidase activity were statistically higher in the Ped group compared to the Mel-Ped group (P <0.05). Immunohistochemical staining of RANKL and osteoclast activity were significantly lower in the Mel-Ped group compared to the Ped group (P <0.05). CONCLUSION: This study reveals that melatonin treatment significantly inhibits regional alveolar bone resorption and contributes to periodontal healing in an experimental periodontitis rat model.

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in kidney of rats treated with gentamicin sulphate.

The protective effects of Panax ginseng (PG) on gentamicin sulphate (GS) induced acute nephrotoxicity were investigated in rats. A total of 32 adult Sprague-Dawley rats were randomly divided into 4 equal groups and treated by intraperitoneous route for 10 days with: 0.5 mL of isotonic saline (group C), GS 100 mg/kg/day (group GS), co treatment PG (100 and 200 mg/kg/day) plus GS (100 mg/kg/day). After the last injection, kidney markers (urea, creatinine and blood urea nitrogen-BUN) and hepatic markers (aspartate aminotransferase-AST, alanine aminotransferase-ALT, gama glutamil transferase-GGT), and biochemical parameters were analyzed using diagnostic kits. Also, kidney changes were evaluated by immunohistochemical and stereological methods. GS treatment induced significant elevation (P < 0.05) in kidney and hepatic markers, most of biochemical parameters, and Bax immunoreactivity as well. However, co treatments with both doses of PG (100 and 200 mg/kg/day) significantly alleviated (P < 0.05) the GS-induced elevations and have partially protected rats from nephrotoxicity (reduction of kidney damage, and of urea, creatinine and BUN concentrations, and of apoptotic index). Both biochemical results and immunohistochemical evidence showed that administration of PG reduced the gentamicin-induced nephrotoxicity.

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4).

The purpose of this study was to investigate possible beneficial effects of Panax ginseng (PG) on carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. CCl(4) challenge elevated serum enzyme activities of liver and some biochemical parameters, but these effects were prevented by the pretreatment of rats with PG. Histologically, a great amount of mononuclear cells infiltration, necrotic cells and few fibroblasts were observed in liver of CCl(4) group. Also, CD68(+) and caspase-3 staining cells were diffused in both lobular and portal areas. However, PG pretreatment had a little influence on the number of caspase-3 immunopositive staining cells in the liver, but CD68(+) staining areas were significantly decreased in the PG+CCl(4) when compared to CCl(4) group. We conclude that PG treatment may play a protective role by enhancing liver enzyme activities and recovering biochemical parameters, and improving the changes in histological structure against CCl(4)-induced liver damages in rats.

Pomegranate seed extract attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in rats.

Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.