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.

Cabazitaxel causes a dose-dependent central nervous system toxicity in rats.

BACKGROUND: Chemotherapeutic agents may lead to serious neurological side effects, which in turn can deteriorate the quality of life and cause dose limiting. Direct toxic effect or metabolic derangement of chemotherapeutic agents may cause these complications. Cabazitaxel is a next generation semi-synthetic taxane derivative, which is effective in both preclinical models of human tumors sensitive or resistant to chemotherapy and in patients with progressive prostate cancer despite docetaxel treatment. AIM: The primary aim of this study was to investigate the central nervous system toxicity of Cabazitaxel. Secondary aim was to investigate the safety dose of Cabazitaxel for the central nervous system. METHODS: A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups as follows: group 1 (Controls), group 2 (Cabazitaxel 0.5mg/kg), group 3 (Cabazitaxel 1.0mg/kg) and group 4 (Cabazitaxel 1.5mg/kg). Cabazitaxel (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to groups 2, 3 and 4 at 0.5, 1.0 and 1.5mg/kg (body-weight/week) doses, respectively for four consecutive weeks. Beside this, group 1 received only i.p. saline at the same volume and time. At the end of the study, animals were sacrificed and bilateral brain hemispheres were removed for biochemical, histopathological and immunohistochemical examinations. RESULTS: Intraperitoneal administration of Cabazitaxel has exerted neurotoxic effect on rat brain. We have observed that biochemical and immunohistochemical results became worse in a dose dependent manner. CONCLUSION: Our findings have suggested that Cabazitaxel may be a neurotoxic agent and can trigger apoptosis in neuron cells especially at high doses.

Selenium protects cerebral cells by cisplatin induced neurotoxicity.

PURPOSE: To evaluate the central nervous system toxicity of cisplatin and neuroprotective effect of selenium. METHODS: Twenty-one male Wistar albino rats were divided into three groups: control (C), cisplatin (CS), cisplatin and selenium (CSE, n=7 in each group). Cisplatin (12 mg/kg/day, i.p.) was administered to CS and CSE groups for three days. Furthermore, CSE group received 3mg/kg/day (twice-a-day as 1.5 mg/kg) selenium via oral gavage five days before cisplatin injection and continued for 11 consecutive days. The same volumes of saline were administered to C group intraperitoneally and orally at same time. RESULTS: Heterochromatic and vacuolated neurons and dilated capillary vessels in the brain were observed in the histochemical examinations of cisplatin treated group. Rats that were given a dose of 3mg/kg/day selenium decreased the cisplatin induced histopathological changes in the brain, indicating a protective effect. In addition, cytoplasmic staining of the cell for bcl-2, both cytoplasmic and nuclear staining for bax were determined to be positive in the all groups. Bax positive cells were increased in the CS group compared to C group, in contrast to decreased bcl-2 positivity. CONCLUSION: Selenium limited apototic activity and histological changes due to the cisplatin related central neurotoxicity.

Selenium protects cerebral cells by cisplatin induced neurotoxicity

PURPOSE: To evaluate the central nervous system toxicity of cisplatin and neuroprotective effect of selenium. METHODS: Twenty-one male Wistar albino rats were divided into three groups: control (C), cisplatin (CS), cisplatin and selenium (CSE, n=7 in each group). Cisplatin (12 mg/kg/day, i.p.) was administered to CS and CSE groups for three days. Furthermore, CSE group received 3mg/kg/day (twice-a-day as 1.5 mg/kg) selenium via oral gavage five days before cisplatin injection and continued for 11 consecutive days. The same volumes of saline were administered to C group intraperitoneally and orally at same time. RESULTS: Heterochromatic and vacuolated neurons and dilated capillary vessels in the brain were observed in the histochemical examinations of cisplatin treated group. Rats that were given a dose of 3mg/kg/day selenium decreased the cisplatin induced histopathological changes in the brain, indicating a protective effect. In addition, cytoplasmic staining of the cell for bcl-2, both cytoplasmic and nuclear staining for bax were determined to be positive in the all groups. Bax positive cells were increased in the CS group compared to C group, in contrast to decreased bcl-2 positivity. CONCLUSION: Selenium limited apototic activity and histological changes due to the cisplatin related central neurotoxicity. .

Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study.

Diabetes mellitus (DM) is one of the most common and chronic diseases, especially in post-menopausal periods. Neuro-degeneration occurs more frequently in post-menopausal diabetics. Therefore, we investigated ovariectomized rats cerebellar cortex response to the estradiol deficiency and hyperglycemia. For the ovariectomy, the rats were bilaterally ovariectomized, and then DM induced by a single dose of Alloxan monohydrate injection in ovariectomy or/and diabetic groups. During light and electron microscopic examination, degenerated Purkinje cells membrane, swollen organelles, degenerated mitochondria, edema formation and vacuolization were seen in the ovariectomy and ovariectomy-diabetic groups sections. In addition, increased apoptotic activity was observed in the ovariectomy and ovariectomy-diabetic groups compared to the control group. We demonstrated that estradiol and insulin deficiency can affect the cerebellar cortex, which support the hypothesis that the execution of neuronal damages in post-menopausal diabetics. Also, diabetes and menopause are major risks factors for many disorders including nervous system and the number of post-menopausal-diabetics are increasing world-wide.

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.

Royal jelly modulates oxidative stress and apoptosis in liver and kidneys of rats treated with cisplatin.

Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ) against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg(-1) body weight i.p., single dose); group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day); group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA), elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.

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.

A stereological and electron microscopic study of the development of the nephron in prenatal and postnatal rats.

OBJECTIVE: To describe the morphometric and ultra-structural features of the kidney in fetal (20-day-old), newborn (7-day-old) and adult (180-day-old) rats. MATERIALS AND METHODS: Kidneys from all animals were excised, fixed in 3% glutaraldehyde in 0.1 M phosphate buffer, post-fixed in 1% phosphate-buffered osmium tetroxide, and examined by stereological and light and electron microscopic methods. RESULTS: Fetal kidneys displayed kidney corpuscles, glomeruli, and proximal and collective tubules at multiple developmental stages. Glomeruli in the outer surfaces of the kidney were less mature than those in the inner surface. Kidney corpuscles were made up of parietal cells and podocytes without feet. Kidneys from newborn rats were almost completely developed, while kidneys in adult rats were fully developed. Under stereological examination, the percent volume of cortex in fetal kidneys (86.19%) was higher than in newborn (53.77%) or adult rats (76.78%). Compared to both newborn and fetal rats, adult rats displayed the highest total volumes of distal and proximal tubules, but lower mean glomerular or Bowman's capsule volumes. On the other hand, the total number of glomeruli was increased in adult rats (32,600) as compared to newborn (17,896) and fetal (11,650) rats. CONCLUSION: These data suggest that development of metanephric kidneys is not yet complete by gestational day 20, but is almost complete at postnatal week one. Furthermore, the developmental stage of the kidney, as determined by stereology, correlates well with the age of the rat.