Histidine, carnosine, and ergothioneine attenuate pyrazole/LPS-induced hepatotoxicity through modulation of CYP2E1, Nrf2, and NF-κB signaling in mice

Protective effect of Dapagliflozin on hepatic encephalopathy induced by thioacetamide in rats: involvement of ERK, JNK, and Nrf2/HO-1 pathways.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with oxidative stress, neuroinflammation, and hyperammonaemia secondary to hepatic dysfunction. This study aimed to investigate dapagliflozin's effects (DAPA) against HE induced by thioacetamide (TAA) in rats and to elucidate the roles of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathways. HE was induced by injection of TAA (200 mg/kg) intraperitoneally 2 times every other day. Two groups were pretreated with DAPA at 5 and 10 mg/kg for 15 days; on the 13th day, rats were given TAA (200 mg/kg, i.p.) twice, 2 days apart. Behavioral assessments, including object recognition and rotarod tests, were conducted, and serum and tissue samples were collected for biochemical and molecular analyses. DAPA pretreatment ameliorated TAA effects, improved recognition memory, enhanced muscular tone and motor coordination. DAPA also reduced ALT (alanine aminotransferase), AST (aspartate aminotransferase), and ammonia serum levels. Additionally, it restored antioxidant balance, decreased malonaldehyde (MDA) and increased reduced glutathione (GSH). Moreover, it reduced tissue inflammation and inhibited apoptosis; where tumor necrosis factor-alpha (TNF-α) and caspase-3 expression were suppressed. DAPA was associated with increased Nrf2/HO-1 pathway-related protein expression while decreasing pERK/total ERK and pJNK/total JNK ratios, along with nuclear factor kappa-light-chain-enhancer of activated B cells, p65 subunit (NF-κB-p65) protein expression. Histopathologically, DAPA improved hepatic and brain architecture. Collectively, DAPA exhibits hepatoprotective and neuroprotective effects against TAA-induced HE accompanied by modulation in oxidative-, inflammatory-, and apoptotic-related protein expression, highlighting its therapeutic potential in hepatic encephalopathy.

Chrysin attenuates pentadecafluorooctanoic acid-induced hepatotoxicity in male Wistar rats via modulation of oxidative stress, inflammation, and metabolic dysfunction

Overall, chrysin demonstrates potent protective potential against PFOA-induced liver injury and may serve as a promising therapeutic candidate for environmental toxin-associated hepatotoxicity.

Hepatoprotective Effects of Nigella sativa and Thymoquinone: Modulation of CYP450 Enzymes and Cytochrome c Reductase in CCl4-Induced Hepatotoxicity.

Mangiferin mitigates mercuric chloride-induced hepatotoxicity: targeting Nrf2, NF-κB, NLRP3, and ER stress.

Man could be considered as a potential protective agent against HgCl2-induced liver injury through controlling oxidative stress, inflammation, and apoptosis.

Epigallocatechin-3-gallate as a hepatoprotective agent against ochratoxin a: modulating ER stress and NF-κB/TNF-α/IL-6 responses

A closer insight into the molecular effect of canagliflozin on gentamicin-induced nephrotoxicity in rats: Attention to SIRT1/Nrf2/HO-1, p38 MAPK/NF-κB signaling pathways, and expression of miR-21 and miR-155.

OBJECTIVE Nephrotoxicity is considered the most detrimental effect of gentamicin (GM). In this study, we investigated the potential effects for canagliflozin (CANA) to protect against GM-induced nephrotoxicity, besides the multiple molecular pathways underlying these effects. METHODS Four groups with six rats in each were used: (1) control; (2) GM (100 mg/kg, intraperitoneal injection) for 7 days; (3) CANA + GM group: Rats were given CANA (10 mg/kg, by oral gavage) for 14 days, and GM (100 mg/kg, by IP) was co-administered with CANA in the last 7 days; and (4) CANA group: Rats were given CANA (10 mg/Kg, by oral gavage) for 14 days. RESULTS Relative to GM-challenged rats, CANA ameliorated GM-induced changes in the state of oxidative stress. Also, CANA alleviated the GM-evoked reduction in the renal expression of SIRT1 and Nrf2. Furthermore, CANA decreased the renal expression of NF-ҡB and reduced p38-MAPK levels in kidneys of GM-treated animals. Simultaneously, GM-induced changes in the renal expression of miR-21 and miR-155 have been successfully amended by CANA. CONCLUSION Altogether, current outcomes imply that modification of the SIRT1/Nrf2/HO-1, the p38-MAPK/NF-ҡB pathways, and microRNAs (miRNAs) play an important role adressing CANA's `protective properties against GM nephrotoxicity.