Background: Acetaminophen (APAP)-induced acute liver injury (ALI) is increasingly becoming a public health issue with high rate of morbidity and mortality. Therefore, there is a critical demand for finding protective modalities by understanding the underlying proposed mechanisms including, but not limited to, ferroptosis and inflammation. Objectives: This study seeks to investigate the possible hepatoprotective effect of empagliflozin (EMPA) against APAP-induced ALI through modulation of ferroptosis and inflammatory cascades. Methods: Mice were allocated into the following five groups: vehicle control, APAP, EMPA 10, EMPA 20 (10 and 20 mg/kg/day, respectively, P.O.), and N-acetylcysteine (NAC, hepatoprotective agent against APAP-induced ALI). The hepatic injury was detected by determining liver enzymes and by histopathological examination. Inflammation, oxidative stress, apoptosis, and ferroptosis were also evaluated. Results: The APAP group showed an elevated level of hepatic enzymes with disrupted hepatic architecture. This toxicity was promoted by inflammation, oxidative stress, apoptosis, and ferroptosis, as indicated by elevated cytokines, lipid peroxidation, reduced antioxidants, increased caspase-3, decreased Bcl-2, and activation of the NF-κB/STAT3/hepcidin pathway. Pretreatment with EMPA remarkably reversed these features, which was reflected by restoration of the histoarchitecture of hepatic tissue, but the higher dose of EMPA was more efficient. Conclusions: APAP can induce ALI through initiation of inflammatory and oxidative conditions, which favor ferroptosis. EMPA hindered these unfavorable consequences; an outcome which indicates its anti-inflammatory, antioxidant, anti-apoptotic, and anti-ferroptotic effects. This modulatory action advocated EMPA as a potential hepatoprotective agent.

Background and Objectives: Pulmonary fibrosis (PF) is an interstitial lung disease that leads to death and is characterized by excessive collagen deposition and tissue scarring. Bleomycin (BLM) is widely used to induce PF in rodent models, closely resembling human idiopathic pulmonary fibrosis. Ivermectin, a broad-spectrum antiparasitic agent, has recently attracted interest due to its reported anti-inflammatory and antifibrotic effects. The beneficial effects of ivermectin to treat PF may be attributed to suppressing the NLRP3 inflammasome. Ivermectin can cause acute toxicity, including convulsions, when overdosed in animals. In humans, it may induce neurological disorders, particularly in individuals with mutations in the ABCB1 gene. This study aimed to investigate the potential protective role of ivermectin against BLM-induced PF in rats. Materials and Methods: Forty adult male albino rats were randomly allocated into four groups (n = 10 each): control, ivermectin-treated (0.6 mg/kg, orally on days 0, 1, 7, and 8), BLM-treated (single intratracheal dose of 5 mg/kg), and BLM- and ivermectin-treated. Lung tissues were collected for histopathological analysis and Mallory trichrome staining to assess collagen deposition. Mast cell (MC) infiltration was assessed using toluidine blue. Immunohistochemistry for α-SMA and Ki-67 was used to evaluate myofibroblast and cell proliferation. Oxidative stress parameters, including serum total antioxidant capacity, lung glutathione and lung nitric oxide were measured. Results: Ivermectin treatment markedly attenuated BLM-induced lung fibrosis, showing reduced collagen accumulation, restoration of alveolar architecture, and decreased inflammatory cell infiltration. Immunohistochemical evaluation revealed decreased expression of α-SMA and Ki-67, while biochemical analyses demonstrated improved oxidative stress markers. Conclusions: Ivermectin significantly mitigates BLM-induced pulmonary fibrosis in rats through modulation of inflammation, suppression of myofibroblast proliferation, and reduction in oxidative stress and collagen deposition. These findings highlight ivermectin as a potential candidate for the management of fibrotic lung diseases, warranting further mechanistic and clinical investigations.