Background and purpose: Hepatotoxicity from frequently prescribed drugs has become an evolving health problem. This study was conducted to evaluate the risk of acute and chronic administration of acetaminophen (AAP), ibuprofen (Ibu), and acetylsalicylic acid (ASA). Methods: One hundred and twenty male albino rats, were divided into 2 main groups for acute and chronic study. Each group was sub-classified into 5 sub-groups (12 rats for each). Acute study: control (normal saline), AAP (single oral dose, 540 mg/kg, bw), AAP +Zn (APP and Zn ,227 mg/liter drinking water 24 hours before AAP administration), Ibu (single oral dose,440 mg/kg, bw), and ASA (single intraperitoneal dose,540 mg/kg, bw). Chronic (period for 60 days): control (normal saline), AAP (single daily doses, 48 mg/kg, bw), AAP +Zn (APP and Zn, 227 mg/liter drinking water for 6o days), Ibu (single daily doses, 48 mg/kg, bw), and ASA (single daily intraperitoneal doses, 40 mg/kg,). Results: Hepatic aminotransferases, alkaline phosphatase, isocitrate dehydrogenase, serum glycosaminoglycans, tissue hydroxyproline, and malondialdehyde were significantly elevated, but glutathione was significantly decreased, in both acute and chronic treatments in all treated groups. Prior treatment with Zn couldn’t change the effects of AAP, except on oxidative stress. Tissue changes after chronic treatment varied from fatty changes to vascular congestions and inflammation. Conclusion: We assume that both acute and chronic administration of AAP, Ibu, and ASA have deleterious hepatotoxic and fibrogenic effects on the liver with a non-significant protective role to Zn co-administration with AAP against oxidative stress.

Excessive acetaminophen (APAP) intake is a major cause of acute liver injury, primarily through its conversion to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which induces oxidative stress and ferroptosis, a form of iron-dependent, lipid peroxidation-mediated cell death. This study investigated the hepatoprotective effects of vitamin K1(Vit K1) and its role in modulating ferroptosis via the Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase-1 (HO-1) antioxidant pathway. Male mice were pretreated with Vit K1 (1, 2, or 3 mg/kg) prior to APAP injection (200 mg/kg). Liver damage was assessed by serum biomarkers Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and albumin, oxidative stress markers including reduced glutathione (GSH), malondialdehyde (MDA) and Nitric Oxide (NO), and ferroptosis indicators glutathione peroxidase 4 (GPX4), hepatic iron, acyl-CoA synthetase Long-chain family member 4 (ACSL4). APAP significantly increased ALT, AST, MDA, NO, and iron, while reducing albumin, GSH, and GPX4 levels, indicating oxidative injury and ferroptosis. Vit K1 pretreatment ameliorated these effects dose-dependently by restoring antioxidant balance, suppressing ACSL4 and Keap1 expression, and upregulating Nrf2 and HO-1. These results suggest that Vit K1 may protect against APAP-induced hepatotoxicity by inhibiting ferroptosis and activating antioxidant responses through the Keap1-Nrf2/HO-1 pathway, supporting its potential as a therapeutic candidate for drug-induced liver injury.

Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous follicles that affects nearly 90% of teenagers; half of them continue to experience symptoms as adults. There have been several reports of monomorphic acneiform eruptions in patients treated with intramuscular cobalamin injections. The eruptions resolved after the cessation of the therapy. Cyanocobalamin, pyridoxine (B6), and riboflavin (B2) have been reported to exacerbate existing acne. Moreover, it was reported that in acne patients, the serum level of vitamin B12 was significantly decreased after treatment, but no explanation was given. We propose a vitamin B12-mediated bacterial mechanism for acne pathogenesis on the evidence mentioned above. One hundred twenty AV patients were recruited. Our results proved that vitamin B12 was involved in the pathogenesis of AV; in vivo, it proved that AV patients had significantly higher serum levels of the vitamin than controls and showed a positive correlation to the disease duration and severity. In vitro, it proved that vitamin B12 supplementation to p. acnes cultures significantly raised the porphyrins produced in these cultures when compared to the non-supplemented ones. It also proved that this shift in the metabolism is secondary to inhibition of the cbiL gene of the vitamin B12 synthesis in the bacteria; as porphyrins and vitamin B12 share the same precursors, vitamin B12 does has a role in either elicitation or aggravation of AV.

Background and aim: Accumulation of heavy metals, such as iron, copper, and lead can be hepatotoxic. This study aimed to investigate the effect of exposure to iron, copper, and lead on the liver, along with an experimental study. Methods: Thirty-six male workers from 3 factories in Egypt (12/each), lead, copper, and iron groups against a control group. Thirty-two rats were classified into 4 groups (8/each), control, iron (given oral ferrous gluconate, 10 mg/kg body weight), copper (given oral copper sulfate, 10 mg/kg body weight), and lead (given intraperitoneal lead acetate,8 mg/kg body weight) daily for 30 days. Results: Human iron, copper, and lead serum levels were non-significantly higher than control. Serum total glycosaminoglycans (TGAGs) and fibronectin (FN) were significantly raised in all workers with significant increases in alkaline phosphatase in iron and copper workers, and aspartate aminotransferase in ironworkers. Experimentally, liver hydroxy proline was significantly elevated, with disturbed tissue oxidative stress, serum liver indices with depressed hepatic tissue TGAG, and fibrosis among metal-loaded rats. Conclusion: The studied workers seem protected against metal intoxication, but non-significant serum increments could predict future hepatic fibrosis, manifested as correlative elevations in serum TGAGs and FN. Disrupted experimental fibro-genic parameters could explain our theory.