Inhibition of endoplasmic reticulum stress and activation of autophagy-protect intestinal and renal tissues from western diet-induced dysbiosis and abrogate inflammatory response to LPS: role of vitamin E.

Diet pattern is an emerging risk factor for renal disease. The mechanism by which high-fat high fructose (western) diet mediates renal injury is not yet fully understood. The objective of the present study was to investigate the relationship between endoplasmic reticulum (ER) stress and autophagy in the development of renal impairment and aggravation of the inflammatory response. Eighty male rats were randomly divided into four groups as follows: a standard diet-fed (ConD), a high-fat high fructose diet fed (HFHF-V), ConD fed and orally supplemented with vitamin E (ConD-E), and HFHF fed and orally supplemented vitamin E (HFHF-E). After 12 weeks, either lipopolysaccharide (LPS) or saline was injected. We found that upregulation of endoplasmic reticulum stress-related proteins rendered the cells susceptible to injury induced by dysbiosis and microbiota-derived metabolites. A downregulation of autophagy and upregulation of caspase-12 resulted in the loss of intestinal integrity and renal tubular injury. Maintained ER stress also increased the inflammatory response to LPS. In contrast, vitamin E effectively ameliorated ER stress and promoted autophagy to protect intestinal and renal tissues. Our results provide insight into the influences of sustained ER stress activation and autophagy inhibition on the development of renal injury, which may contribute also to the enhanced inflammatory response.

The ameliorative effect of curcumin on cryptorchid and non-cryptorchid testes in induced unilateral cryptorchidism in albino rat: histological evaluation.

BACKGROUND: Cryptorchidism, one or both hidden testes, is the most common abnormality of male sexual development. Subfertility or infertility is associated with both unilateral and bilateral cryptorchidism. In this study, we investigate the possible ameliorative effect of curcumin (Cur) on the induced-unilateral cryptorchidism testicular injury in both cryptorchid (Cryp) and non-cryptorchid (non-Cryp) scrotal testes through histological, immunohistochemical and morphometrics. MATERIALS AND METHODS: Forty adult male albino rats were divided into: control group, Cur control group, Cryp group, and Cryp+Cur group. The rat model was surgically established by fixing the left testis in the abdomen. The treated groups were subjected to surgically induced-unilateral cryptorchidism on the left side then were given Cur (80 mg/kg) orally, for 20 days. Histological analysis using haematoxylin and eosin and periodic acid Schiff's reaction was done. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA); to estimate the proliferation in the germinal epithelium, and vimentin; to evaluate Sertoli cells. The results were confirmed by statistical evaluation of the spermatogenic epithelium height, the seminiferous tubules diameter, the basement membrane thickness, the number of PCNA immunostained cells and the area per cent of vimentin immunostaining. RESULTS: Distorted seminiferous tubules, substantial degeneration of the germinal epithelium, thickening of the basement membrane with a significant decrease in PCNA and vimentin immunostaining were observed in Cryp group; mainly in the cryptorchid testis. These structural changes were significantly reversed in Crypt+Cur group. CONCLUSIONS: Curcumin proved to be an important and effective medical line for protecting against the unfavourable sequels of cryptorchidism in a rat model.