N-Acetyl-p-aminophenol (APAP) or acetaminophen is the most common drug ingredient worldwide. It is found in more than 600 different over-the-counter and prescription medicines. Its long-term and overdose use is highly toxic and may result in liver injury. Thus, this study was designed to assess the preventive effects and to suggest the mechanisms of action of the navel orange peel hydroethanolic extract, naringin, and naringenin in APAP-induced hepatotoxicity in male Wistar rats. APAP was administered to male Wistar rats at a dose level of 0.5 g/kg body weight (b.w.) by oral gavage every other day for 4 weeks. APAP-administered rats were treated with the navel orange peel hydroethanolic extract (50 mg/kg b.w.), naringin (20 mg/kg b.w.), and naringenin (20 mg/kg b.w.) by oral gavage every other day during the same period of APAP administration. The treatments of APAP-administered rats with the peel extract, naringin, and naringenin produced a significant decrease in the elevated serum AST, ALT, ALP, LDH, and GGT activities as well as total bilirubin and TNF-α levels while they induced a significant increase in the lowered serum albumin and IL-4 levels. The treatments also resulted in a significant decrease in the elevated liver lipid peroxidation and enhanced the liver GSH content and SOD, GST, and GPx activities as compared with APAP-administered control; the peel extract was the most potent in improving the liver LPO, GSH content, and GPx activity. In addition, the three treatments significantly downregulated the elevated hepatic proapoptotic mediators p53, Bax, and caspase-3 and significantly upregulated the suppressed antiapoptotic protein, Bcl-2, in APAP-administered rats. In association, the treatments markedly amended the APAP-induced liver histopathological deteriorations that include hepatocyte steatosis, cytoplasmic vacuolization, hydropic degeneration, and necrosis together with mononuclear leucocytic and fibroblastic inflammatory cells’ infiltration. In conclusion, the navel orange peel hydroethanolic extract, naringin, and naringenin may exert their hepatopreventive effects in APAP-administered rats via enhancement of the antioxidant defense system and suppression of inflammation and apoptosis.

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Mesoporous silica nanoparticles (MSNs) represent a promising inorganic platform for multiple biomedical applications. Previous studies have reported MSNs-induced hepatic and renal toxicity; however, the toxic mechanism remains unclear. This study aimed to investigate MSNs-induced hepatic and nephrotoxicity and test the hypothesis that altered TLR4/MyD88/NF-κB, JAK2/STAT3, and Nrf2/ARE/HO-1 signaling pathways mediate oxidative stress, inflammation, and fibrosis induced by MSNs. Rats were administered 25, 50, 100, and 200 mg/kg MSNs for 30 days, and samples were collected for analyses. MSNs induced functional and histologic alterations, increased the levels of reactive oxygen species (ROS), lipid peroxidation and nitric oxide, suppressed antioxidants, and Nrf2/HO-1 signaling in the liver and kidney of rats. MSNs up-regulated the expression of liver and kidney TLR4, MyD88, NF-κB p65, and caspase-3 and increased serum pro-inflammatory cytokines. In addition, MSNs activated the JAK2/STAT3 signaling pathway, down-regulated peroxisome proliferator activated receptor gamma (PPARγ), and promoted fibrosis evidenced by the increased collagen expression and deposition. In conclusion, this study conferred novel information on the role of ROS and deregulated TLR4/MyD88/NF-κB, JAK2/STAT3, PPARγ, and Nrf2/ARE/HO-1 signaling pathways in MSNs hepatic and nephrotoxicity. These findings provide experimental evidence for further studies employing genetic and pharmacological strategies to evaluate the safety of MSNs for their use in nanomedicine.

This study was performed for the purpose of investigating the prevalence of Sarcocystis spp. in buffaloes in Beni-Suef Governorate, Egypt. Both macroscopic (Sarcocystis fusiformis) and microscopic (Sarcocystis levinei) cysts were recognized, and were differentiated by their morphological features and location in the tissues. Of 379 buffaloes examined in abattoirs in Beni-Suef, 299 were found to be infected, with an overall prevalence of 78.9%. Depending on age, three categorized groups of naturally infected buffaloes were examined: male buffalo calves aged 1.5-2 years, adult females aged 2-5 years, and females older than 5 years. Among these groups, infection rates were 74.5%, 82.3%, and 81.2%, respectively. Organs examined included esophagus, tongue, and heart. Macroscopic cysts were examined by the naked eye through meat inspection in abattoirs, while the pepsin-digestion method and the histological technique were applied to detect microscopic cysts. It has been found that esophagus showed the highest rate of infection among the infected organs, with both macroscopic and microscopic cysts seen in the infected buffaloes. Moreover, results of the pepsin-digestion method proved more accurate than those produced by the histological technique in terms of infection rates for the microscopic cysts. Our findings indicated that infected buffaloes aged 2-5 years showed the highest mixed infection rate (82.3%) for both types of cysts. The high prevalence of microscopic Sarcocystis spp. in Beni-Suef Governorate reflects a significant role played by stray dogs, rather than cats, in the transmission of these parasites.