Protective Role of Ferulic acid and/or Gallic acid Against Pulmonary Toxicity Induced by Amiodarone in Rats

Amiodarone is an orally active antiarrhythmic drug generally used throughout the world, causing pulmonary toxicity as one of its most harmful side effects. The efficacy of two phenolic acids; ferulic acid FA or gallic acid GA or their combination on the lung injury in amiodarone-induced lung toxicity were clarified. Fifty albino rats were divided into five groups as follows; G1: Healthy control kept without treatment, G2: Amiodarone group, rats were administered by Amiodarone AD in a daily oral dose (30 mg/kg bw)by gastric gavage for 6 weeks to induce pulmonary toxicity.G3: AD+FA, after induction of pulmonary toxicity, rats received an oral daily dose of FA (100 mg/kg bw) for 6 consecutive weeks. G4: AD + GA, after induction of pulmonary toxicity, rats received an oral daily dose of GA (200 mg/kg.bw) for 6 consecutive weeks. G5: AD + FA+GA, rats have received Amiodarone and a mixture of GA (200 mg/kg bw) and FA (100 mg/kg.bw) for 6 consecutive weeks. Lung samples were assayed for oxidative stress and inflammatory biomarkers along with lung histology and DNA comet assay. The study found that AD causes pulmonary toxicity manifested by a significant alteration in serum level of Lung Na⁺-K⁺ adenosine triphosphatase, lung tissue content of antioxidant enzymes, and inflammatory biomarkers. Also, lung DNA damage was indicated as a significant change in comet assay parameters, in addition to histological alterations. Results showed that oral administration of FA, GA, or a combination of them reversed these biochemical indices, such as histopathological alterations and DNA damage induced by AD. These findings designated that FA and GA have defensive effects against AD-induced pulmonary toxicity due to its anti-inflammatory and antioxidant properties. GA or a combination of both FA and GA has the most potent effect on inflammatory biomarkersand oxidative stress.Therefore, supplementingGA and FA combination as an adjuvant remedypossibly be a promising compound in lowering AD side effects.