Pentoxifylline mitigates CCl4-induced liver damage in rats: integrated biochemical, hematological, histopathological, and correlation heatmap analysis

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.

The Effect of Curcumin on Carbon Tetrachloride-Induced Lung Injury

Background/Objectives: Carbon tetrachloride (CCl4) is a potent toxic agent that induces oxidative stress, inflammation, fibrosis, and apoptosis in various tissues, including the lungs. This study aimed to investigate the potential protective effects of curcumin against CCl4-induced lung injury in rats using histopathological, biochemical, and immunohistochemical analyses. Methods: A total of 40 male Wistar albino rats were allocated to four experimental groups: control, curcumin, CCl4, and CCl4 + Cur. Curcumin was administered orally at 200 mg/kg/day for three weeks, whereas CCl4 was administered intraperitoneally at 0.5 mL/kg as a 1:1 mixture with olive oil every other day for three weeks. Results: Histopathological examination revealed marked alveolar septal thickening, hemorrhage, vasocongestion, inflammatory cell infiltration, vacuolization, and epithelial desquamation in the CCl4 group, whereas lung tissue architecture was largely preserved in the CCl4 + Cur group. Biochemically, CCl4 exposure significantly increased the MDA levels and decreased SOD activity, while curcumin administration significantly reduced the MDA levels and increased SOD activity. Immunohistochemical H-score analysis showed significantly higher TNF-α, IL-1β, TGF-β, and caspase-3 immunoreactivity in the CCl4 group, whereas these alterations were significantly reduced following curcumin administration. Conclusions: These findings indicate that curcumin attenuated pulmonary histopathological, biochemical, and immunohistochemical alterations associated with CCl4 exposure, accompanied by improved oxidant–antioxidant balance and reduced inflammatory, profibrotic, and apoptotic immunoreactivity. However, because hepatic injury was not evaluated, the relative contributions of direct pulmonary effects and indirect liver-mediated systemic effects could not be determined.

Loganin Alleviates CCl4-Induced Acute Liver Injury by Promoting Mitophagy and Inhibiting NLRP3 Inflammasome

Remifentanil attenuates LPS-induced hepatic injury by modulating NRF2/HO-1 and necroptosis-related gene expression.

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.

Revisiting two-stage models of chemically-induced cirrhosis-associated hepatocarcinogenesis in rodents: methodological and histopathological approaches

Repeated exposure to hepatotoxins such as carbon tetrachloride (CCl4), thioacetamide (TAA), or diethylnitrosamine (DEN) has been frequently used to induce fibrosis/cirrhosis in rodents. In this narrative review, we compared two-stage medium-term protocols using different CCl4 or TAA regimens in DEN-initiated rats and mice. In addition, we revisited our previous two-stage DEN/CCl4 or DEN/TAA rat models to compare fibrosis grade, the mean number, and the percentage of liver area occupied by hepatocellular lesions positive for placental glutathione S-transferase (GST-P). Thus, we evaluated two groups of male Wistar rats that received DEN (a single dose), as an initiator agent for liver carcinogenesis, followed by CCl4 or TAA regimens (multiple doses) until week 25. Both male Wistar groups presented lower body weight gain and higher liver weight, serum alanine aminotransferase (ALT) levels, hepatocyte proliferation, and a frank development of fibrosis/cirrhosis, GST-P-positive preneoplastic lesions, and liver tumors. However, DEN/TAA protocol in male Wistar rats was more effective as a fibrosis/cirrhosis-associated hepatocarcinogenesis model since TAA effectively accelerates liver disease progression and carcinogenesis. In addition, these chemical regimens have been prospectively studied as a suitable and effective protocol that resembles the corresponding human disease with various molecular and morphological outcomes. In conclusion, two-stage DEN/CCl4 or DEN/TAA rodent models are effective in mimicking the progression of fibrosis-associated hepatocarcinogenesis and are suitable for prophylactic or therapeutic investigations.