Crocin attenuates CCl4-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats.

BACKGROUND: Liver fibrosis is a chronic pathological condition with a leading cause of liver-related mortality worldwide. In the present study, we have evaluated the antifibrotic effect of crocin, a carotenoid present in the stigma of Crocus sativus, and also explored its putative mechanism of action. METHODS: Liver fibrosis was induced by intraperitoneal administration of 30% carbon tetrachloride (CCl4). The crocin was administered orally at 20, 40 and 80 mg/kg body weight along with CCl4 up to 8 weeks. RESULTS: Chronic exposure to CCl4 resulted in elevated levels of liver enzymes and reduced cytochrome P450 2E1 (CYP2E1) activity in the liver. The liver tissue showed cellular swelling, vacuolization, necrosis, infiltration of inflammatory cells and fibrotic changes. The crocin treatment significantly lowered the levels of liver enzymes in serum and improved the liver CYP2E1 mRNA levels. The pathological changes in the liver were also lowered by crocin treatment. The level of pro-inflammatory cytokines, nuclear factor-kappa B, interleukin-6 and tumor necrosis factor α and fibrogenic factor, transforming growth factor ß, and α-smooth muscle actin were elevated by the CCl4 in the liver tissue. However, crocin treatment at different doses significantly reduced the expression of these factors. The increased caspase 3/7 activity was also lowered by crocin. CCl4 administration decreased the expression of peroxisome proliferator-activated receptor γ (PPAR-γ) in liver tissue. The improved PPAR-γ expression in the liver by crocin treatment indicates its role in the therapeutic effect of crocin. CONCLUSIONS: Crocin attenuated the various events in the progression of liver fibrosis via PPAR-γ mediated modulation of inflammatory and fibrogenic pathways.

Antioxidant and hepatoprotective effect of polyphenols from apple pomace extract via apoptosis inhibition and Nrf2 activation in mice.

Industrial apple pomace, a biowaste generated during apple processing, is rich in cell wall polysaccharides and phenolics. These biologically active compounds are reported to be highly beneficial from the nutritional and health point of view. In the present study, the total phenolic content in the apple pomace aqueous extract (APE) was estimated and evaluated for its possible antioxidant and hepatoprotective efficacy in carbon tetrachloride (CCl4)-induced liver injury mice model. The aqueous extract exhibited 2,2-diphenyl-2-picrylhydrazyl free radical scavenging activity in vitro. Under in vivo study, mice were treated with APE (200 mg and 400 mg/kg body weight) for 2 weeks prior to the administration of CCl4 (30% v/v). The serum liver injury markers alanine transaminase, aspartate transaminase, and alkaline phosphatase were significantly lowered by APE in a dose-dependent manner. The levels of antioxidant parameters superoxide dismutase (SOD), reduced glutathione (redGSH), and lipid peroxidation were also improved by APE in liver homogenate. Histopathological studies revealed that APE treatment significantly lowered the CCl4-induced necrotic changes in the liver. Furthermore, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling assay showed that CCl4-induced apoptosis in the liver was significantly inhibited by APE in a dose-dependent manner. Immunohistochemistry results showed higher expression of nuclear erythroid 2-related factor 2 (Nrf2) in the liver of the APE-treated mice, a key regulator of antioxidative response. In conclusion, the results of the present study revealed the hepatoprotective efficacy of APE by inhibiting CCl4-induced apoptosis, which is due to its antioxidant activity and the ability to induce Nrf2 protein expression.

Pathology of ochratoxin A-induced nephrotoxicity in Japanese quail and its protection by sea buckthorn (Hippophae rhamnoides L.).

The present study was designed to study the protective effect of sea buckthorn (SBT) against renal damage induced by ochratoxin A (OTA) in Japanese quail. Day-old quail chicks were divided into six groups and fed a basal quail chick mash containing 2% SBT leaf powder (group SX), OTA at a dietary level of 3 ppm (group OX), 25 ppm L-beta-phenylalanine (Phe) plus 3 ppm OTA (group OP), 2% dietary level of SBT leaf powder plus 3 ppm OTA (group OS), SBT leaf extract at a level of 10%/L of drinking water plus 3 ppm OTA (group OSS), and a standard toxin-free feed (group CX, control) for 21 days. OTA at 3 ppm level in diet grossly revealed mild to moderate renal swelling in OX birds, and the severity was less in the case of OS, OSS, and OP birds. Microscopically, degenerative, necrotic, and inflammatory changes were observed in OX birds, but the changes were less severe in OS, OSS, and OP birds. Ultrastructural studies revealed remarkable and consistent changes in the proximal convoluted tubules (PCTs), with severe damage of mitochondria and endoplasmic reticulum in OX birds, whereas SBT-treated birds (groups OS, OSS) had mild changes in mitochondria. A moderate to marked increase in number of peroxisomes in the cytoplasm of PCTs was a consistent finding in the Phe- and SBT-treated groups kept on OTA in comparison to the group fed OTA alone. In conclusion, the inclusion of 2% SBT leaf powder in feed and SBT leaf extract in water provided partial protection against OTA-induced nephropathy in Japanese quail.