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Tert-butylhydroquinone prevents cyclophosphamide induce lung toxicity in rats via inhibiting oxidative stress and apoptosis: in vivo and in silico study

Author name : Ibrahim Khalifa Mohamed Athar
Publication Date : 2024-05-07
Journal Name : Egyptian Journal of Forensic Sciences

Abstract

Background
Cyclophosphamide (CP) is a chemotherapeutic and immunosuppressive agent that induces oxidative stress, causing lung tissue damage.

Aim
The study aims to explore the antioxidant role of tert-butylhydroquinone (TBHQ) in ameliorating CP-induced lung toxicity exhibited as oxidative stress and programmed cell death.

Methods
Thirty-two adult male rats were allocated randomly into four groups: group 1 (control), group 2 TBHQ 50 mg/kg orally for 14 days, and group 3 single dose of (200 mg/kg, CP, i.p.) on the 9th day. In group 4, TBHQ (50 mg/kg, orally) was provided for 14 days, and (200 mg/kg, CP, i.p.) was administrated on the 9th day. Rats’ body and lung weight were measured. Oxidative stress marker malondialdehyde (MDA) and pulmonary tissue enzymatic antioxidant levels were assessed: glutathione S transferase, catalase, superoxide dismutase, and glutathione peroxidase. Additionally, glutathione level was measured. Assessment of the levels of TNF-α, IL-1β, and IL-6 were done as well as histopathological and immunohistochemistry investigations. Molecular docking studies of the protein structures of p53-MDM2, IL-6, and IL-1β were performed.

Results
CP-intoxicated rats demonstrated a significant decline (CAT, GPx, SOD, GST, and GSH) levels and a significant increase in MDA levels. The proinflammatory parameters (TNF-α, IL-6, IL-1ß) were significantly elevated in group 3. The noted biochemical changes, accompanied by histopathological destruction, indicate CP-induced pulmonary tissue injury. TBHQ played a protective role by attenuating most of the aforementioned biochemical alterations and histopathological distortions in rats’ lungs.

Conclusions
TBHQ might be utilized as a potential ameliorative agent to inhibit CP-induced pulmonary toxicity via TBHQ’s antioxidant and anti-inflammatory effects.

Keywords

Tert-butylhydroquinone ; cyclophosphamide

Publication Link

https://doi.org/10.1186/s41935-024-00395-0

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