Quercetin ameliorates the hepatic apoptosis of foetal rats induced by in utero exposure to fenitrothion via the transcriptional regulation of paraoxonase-1 and apoptosis-related genes

Abstract

Background & purpose

Exposure to organophosphorus during different phases of pregnancy induces many adverse impacts on the developing foetuses due to their immature detoxification system. We have estimated the potential amelioration role of quercetin against hepatic injury-induced apoptosis in rat foetuses following gestational exposure to fenitrothion and probable involvement of paraoxonase-1.

Methods

Forty pregnant rats were allocated into four groups; the first one kept as control, the second intubated with quercetin (100 mg/kg), the third orally administrated fenitrothion (4.62 mg/kg) and the last group received quercetin two hours before fenitrothion intoxication.

Results

Fenitrothion significantly elevated the foetal hepatic levels of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide, but it reduced the enzymatic activities of glutathione-S-transferase, superoxide dismutase, catalase, and acetylcholinesterase. Furthermore, fenitrothion provoked many histopathological changes in the foetal liver and markedly up-regulated the mRNA gene expression of p53, caspase-9 along with elevation in the immunoreactivity of Bax and caspase-3, but it down-regulated the expression level of paraoxonase-1. Remarkably, quercetin co-treatment successfully ameliorated the hepatic oxidative injury and apoptosis prompted by fenitrothion.

Conclusions

Dietary supplements with quercetin can be used to reduce the risk from organophosphorus exposure probably through paraoxonase-1 up-regulation and enhancement of the cellular antioxidant system.

Keywords:

• Fenitrothion
• paraoxonase-1
• oxidative injury
• apoptosis
• quercetin

Ethical approval

The study protocols were approved by Institutional Animal Care and Use Committee-Cairo University (CU/I/F/23/19).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Authors contributions

Khairy A. Ibrahim and Mohammed Eleyan contributed to the study conception and design, material preparation, data collection, and analysis. Mohammed Eleyan and Heba Ali Abd El-Rahman acquired and analysed the data regarding the histological and immunohistochemical examinations. Soad A. Khwanes and Rania A. Mohamed contributed to the data analysis and the first draft of the manuscript. Khairy A. Ibrahim contributed to the obtained data interpretation writing, review, and editing of the manuscript. All authors read and approved the final version of the manuscript.