Histopathological and Molecular Changes During Apoptosis Produced by 7H-Dibenzo[c,g]-Carbazole in Mouse Liver

Abstract

The topical administration of 7H-dibenzo [c,g]carbazole (7H-DBC) at very low but repeated doses causes genotoxic effects such as DNA adduct formation and produces hepatocellular apoptosis in mouse liver. The purpose of this work was to investigate the alterations in gene expression and protein levels of biomarkers associated with the p53 pathway in mouse liver after exposure to cumulative low doses of 7H-DBC by skin paint applications. The compound was administered topically at the dose of 13.35 µg per animal every 2 days to give either 6, 8, 10, or 12 applications. Animals were sacrificed 48 hours after the different treatments. The apoptotic index increased with the number of applications, with a major proportion of apoptotic cells in the periportal areas. A significant increase of Bax mRNA and protein expression was observed after the 8th application whereas the expression of mRNA levels of Fas and p53 did not show significant differences between treated and control animals. Nuclear staining of p53 was detected in hepatocyte nuclei showing the activation of this protein. Later in the apoptosis process we observed the up-regulation of TGF-β1 in parenchymal cells. In addition to the induction of the p53 apoptosis pathway in vivo by 7H-DBC, we have observed molecular changes related to cell proliferation such as the overexpression of the antiapoptotic gene Bcl-2.

Resveratrol mitigates diclofenac‐induced hepatorenal toxicity in rats via modulation of miR‐144/Nrf2/GSH axis

“…Previous studies also reported diclofenac‐induced toxicity to these organs. [ 31–35 ] However, administration or coadministration of resveratrol normalized these adverse impacts of the abovementioned irregularities, demonstrating resveratrol's ability to counter tissue damage caused by diclofenac.…”

“…NF‐κB, TNF‐α, and caspase‐3 protein levels in liver and kidney sections were examined as described by Martín‐Burriel et al [ 30 ] Sections were incubated with primary antibodies against NF‐κB, TNF‐α, and caspase‐3 (1:100 dilutions) (Santa Cruz Biotechnology Inc.). Immune reactions were visualized using diaminobenzidine tetrachloride (DAB, Sigma Chemical Co.).…”

“…NF-κB, TNF-α, and caspase-3 protein levels in liver and kidney sections were examined as described by Martín-Burriel et al [30] Sections were incubated with primary antibodies against NF-κB, TNF-α, and caspase-3…”

Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in Mice

“…Caspase-3, Bax, and CK expression levels in cardiac sections were examined according to the method by Martín-Burriel et al [ 59 ]. Sections were incubated with primary antibodies against caspase-3 (1:100 dilution), Bax (1:100 dilution), and CK (1:50 dilution) (Santa Cruz Biotechnology Inc., Dallas, TX, USA).…”

Comparative Study between Saffron (Crocus sativus L.) and / or Turmeric (Curcuma longa L.) Extracts on D-galactose Deleterious Brain Effects in Rats

“…Caspase-3 activity and Bax expression level in cerebral cortices and hippocampus sections were examined according to Matsushita et al and Martín-Burriel et al [37,38],using(Santa Cruz Biotechnology Inc., Dallas, TX, USA). The immune reaction was visualized using di-aminobenzidine tetrachloride (DAB, Sigma Chemical Co., St. Louis, MO, USA).…”