The present study evaluated the effects of curcumin on epithelial cell apoptosis, the immunoreactivity of the phospho-c-Jun N-terminal kinase (JNK) and phospho-p38 mitogen-activated protein kinases (MAPKs) in inflamed colon mucosa, and oxidative stress in a rat model of ulcerative colitis induced by acetic acid. Rats were randomly divided into three groups: control, acetic acid, and acetic acid+curcumin. Curcumin (100 mg/kg per day, intragastrically) was administered 10 days before the induction of colitis and was continued for two additional days. Acetic acid-induced colitis caused a significant increase in the macroscopic and microscopic tissue ranking scores as well as an elevation in colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and the number of apoptotic epithelial cells in colon tissue compared to controls. In the rat colon, immunoreactivity of phospho-p38 MAPK was increased, whereas the phospho-JNK activity was decreased following the induction of colitis. Curcumin treatment was associated with amelioration of macroscopic and microscopic colitis sores, decreased MPO activity, and decreased MDA levels in acetic acid-induced colitis. Furthermore, oral curcumin supplementation clearly prevented programmed cell death and restored immunreactivity of MAPKs in the colons of colitic rats. The results of this study suggest that oral curcumin treatment decreases colon injury and is associated with decreased inflammatory reactions, lipid peroxidation, apoptotic cell death, and modulating p38- and JNK-MAPK pathways.

We evaluated the effects of L-carnitine on apoptosis of germ cells in the rat testis following irradiation. Male Wistar rats were divided into three groups. Control group received sham irradiation plus physiological saline. Radiotherapy group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiotherapy + L-carnitine group received scrotal irradiation plus 200 mg/kg intraperitoneally L-carnitine. Twenty-four hours post-irradiation, the rats were sacrificed and testes were harvested. Testicular damage was examined by light and electron microscopy, and germ cell apoptosis was determined by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) technique. Morphologically, examination of irradiated testis revealed presence of disorganization and desquamation of germinal cells and the reduction in sperm count in seminiferous tubule lumen. Under electron microscopy, the morphological signs of apoptosis were frequently detected in spermatogonia. Apoptotic spermatogonia showed the marginal condensation of chromatin onto the nuclear lamina, nucleus and cytoplasm shrinkage and still functioning cell organelles. TUNEL-positive cells were significantly more numerous in irradiated rats than in control rats. L-carnitine treatment significantly attenuated the radiation-induced morphological changes and germ cell apoptosis in the irradiated rat testis. In conclusion, these results suggested that L-carnitine supplementation during the radiotherapy may be beneficial for spermatogenesis following testicular irradiation by decreasing germ cell apoptosis.

Curcumin has several biological functions particularly antioxidant and anti-inflammatory. The aims of this study are determination of the protective effects of curcumin on cisplatin-induced renal tubular cell apoptosis and related pathways in kidney. Eighteen male Wistar albino rats were randomly divided into three groups (n ¼ 6): the control, cisplatin (CP), and cisplatin þ curcumin (CP þ CUR). Acute renal damage was induced by single dose of cisplatin (7.5 mg/ kg) injected by intraperitoneally (i.p). The animals of curcumin-treated group were received daily 200 mg/kg curcumin per os (po), starting from 2 days before the injection of cisplatin to the day of sacrifice. Forty-eight hours after cisplatin injection, samples of cardiac blood and kidneys were harvested from the animals. In this study, the major finding is that curcumin treatment ameliorates the following conditions associated with cisplatin-induced nephrotoxicity: (1) the development of kidney injury (histopathology), (2) inflammatory responses [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-a), interleukin-1 beta (IL-1b), IL-6, IL-10 levels], (3) the degree of lipid peroxidation [malondialdehyde (MDA) level], (4) renal tubular cell apoptosis (active caspase-3) and expression of related proteins [p53, Fas, and Fas ligand (Fas-L)] by immunohistochemistry, (5) renal dysfunction (serum urea and creatinine). In a conclusion, this study suggests that curcumin has antiapoptotic effect against cisplatin nephrotoxicity, in addition to anti-inflammatory and antioxidant properties. ARTICLE HISTORY

The present study, we hypothesized that L-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (gamma)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + L-carnitine group received scrotal gamma-irradiation plus 200 mg/kg i.p. L-carnitine. L-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of gamma-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, L-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy.

PURPOSE:To evaluate the alterations of two mitogen-activated protein kinases (MAPK)s, extracellular signal regulated kinase (ERK) and c-Jun NH2 terminal kinase (JNK), in the testes of male rats with experimental diabetes. METHODS:Twenty males Sprague-Dawley rats were randomly divided into a control group (n=8) and a diabetes group (administration of 40 mg/kg/day streptozotocin (STZ) for five sequential days, n=12). After six weeks, testicular biopsy samples were obtained for light microscopy and immunohistochemical methods. RESULTS:The PCNA (proliferating cell nuclear antigen) index was significantly decreased in the diabetes group (p=0.004) when compared to the control group. Both total (t)-ERK and phosphor (p)-ERK immunoreactivities were significantly decreased in the diabetes group (p=0.004, p<0.001, respectively). The t-JNK immunoreactivity was unchanged in both groups (p=0.125), while p-JNK immunoreactivity was significantly increased in the diabetic group (p=0.002). CONCLUSIONS:The decrease of androgen levels in the course of diabetes may contribute to the decrease of the immunoreactivities of t-ERK and p-ERK. JNK may be activated due to the changes in various cytokines and chemochines that participate in the oxidative stress process of diabetes. Therefore, testicular apoptosis may occur and lead to infertility associated with diabetes.