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Abstract Background: Paracetamol (PAR) and diclofenac (DF) are two of the most popular consumed analgesics and anti-inflammatory medications. Objective: This study aimed to explore the protective effect of betanin (Bet) against PAR or DF induced multiple cellular damage in rats.Materials and methods: Rats were randomly divided into five groups: Normal control (NC) group rats were given saline only. PAR group rats received PAR (400 mg/kg). PAR/ Bet treated group rats administered PAR plus Bet (25mg/kg). DF group rats received DF (10mg/kg). DF/ Bet treated group rats administered the same previous doses of DF plus Bet. All drugs were given orally by gastric gavage for 28 consecutive days.Results: PAR and DF caused a marked reduction in brain neurotransmitters, thyroid axis hormones, and testosterone serum levels, as well as induced liver and kidney injury, disrupted serum lipid profile, enhanced serum levels of inflammatory and oxidative stress markers, triggered DNA fragmentation and caused drastic changes in the histopathological pictures of brain, liver, and kidney tissues. Bet supplementation succeeded to ameliorate most of the biochemical changes and protected DNA from damage as obtained from comet assay and improved the histopathological features. Conclusion: The foregoing findings accentuated the potential antioxidant and anti-inflammatory effect of Bet against PAR or DF overconsumption |