Coenzyme Q10 mitigates methotrexate induced salivary gland injury via antioxidant and anti-inflammatory mechanisms

Methotrexate (MTX) is widely used as a chemotherapeutic and immunosuppressive agent; however, its clinical use is often associated with salivary gland (SG) toxicity, primarily mediated by oxidative stress and inflammatory responses. Coenzyme Q10 (CoQ10), a potent antioxidant, has been proposed as a protective agent against drug-induced tissue injury. This study aimed to evaluate the protective effect of CoQ10 against MTX-induced SG damage through biochemical, histological, and ultrastructural assessments. Forty adult male rats were randomly divided into four groups: control, CoQ10-treated, MTX-treated, and MTX + CoQ10-treated groups. MTX was administered intraperitoneally at 20 mg/kg/week, while CoQ10 was given orally at 100 mg/kg/day for 6 weeks. Oxidative stress markers: Malondialdehyde (MDA) and Nitric oxide (NO), antioxidant parameters: Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and pro-inflammatory cytokines:tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were assessed. Histological examination was performed using H&E and Masson’s trichrome staining, as well as scanning and transmission electron microscopy (SEM and TEM, respectively). MTX administration induced significant oxidative stress, evidenced by increased MDA and NO levels, decreased antioxidant enzyme activities, and elevated TNF-α and IL-6 levels ( p < 0.05). Histological analysis revealed severe acinar degeneration, inflammatory infiltration, and increased collagen deposition. SEM and TEM findings confirmed marked structural and ultrastructural alterations. CoQ10 co-administration significantly ameliorated these changes, restoring antioxidant balance, reducing inflammation, and improving glandular architecture and cellular ultrastructure ( p < 0.05). Coenzyme Q10 exerts a protective effect against MTX -induced SG toxicity through its antioxidant and anti-inflammatory properties. These findingssuggest therapy to mitigate MTX-related oral complications. SG dysfunction is a clinically significant complication associated with MTX therapy, often leading to xerostomia, impaired oral function, and reduced quality of life. The present findings suggest that CoQ10, through its antioxidant and anti-inflammatory properties, may offer a protective strategy against MTX-induced SG damage. The observed preservation of glandular architecture and reduction in oxidative and inflammatory markers highlight the potential of CoQ10 as a supportive adjunct in patients undergoing methotrexate treatment. Incorporating CoQ10 supplementation may help minimize oral complications and improve patient comfort and treatment outcomes. However, further clinical studies are required to validate these findings and to establish optimal dosing regimens and long-term safety in human subjects.