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This study aimed to investigate the effectiveness of curcumin (CCM) against gentamicin (GEN) and sodium salicylates (NaS)-induced ototoxic effects in rats. For 15 consecutive days, seven rat groups were given 1 mL/rat physiological saline orally, 1 mL/rat olive oil orally, 50 mg/kg bwt CCM orally, 120 mg/kg bwt GEN intraperitoneally, 300 mg/kg bwt NaS intraperitoneally, CCM+GEN, or CCM+NaS. The distortion product otoacoustic emission measurements were conducted. The rats’ hearing function and balance have been behaviorally assessed using auditory startle response, Preyer reflex, and beam balance scale tests. The serum lipid peroxidation and oxidative stress biomarkers have been measured. Immunohistochemical investigations of the apoptotic marker caspase-3 and the inflammatory indicator nuclear factor kappa (NF-κB) in cochlear tissues were conducted. GEN and NaS exposure resulted in deficit hearing and impaired ability to retain balance. GEN and NaS exposure significantly decreased the reduced glutathione level and catalase activity but increased malondialdehyde content. GEN and NaS exposure evoked pathological alterations in cochlear and vestibular tissues and increased caspase-3 and NF-κB immunoexpression. CCM significantly counteracted the GEN and NaS injurious effects. These outcomes concluded that CCM could be a naturally efficient therapeutic agent against GEN and NaS-associated ototoxic side effects. Graphical abstract

Tulathromycin is a new injectable macrolid antibiotic used for treating pulmonary disease. Therefore, the present work was aimed to study the effect of tulathromycin administration only or in a combination with vitamin C (immunomodatory agent) on immnomodulating, apoptotic effect and DNA of some immune cells. Moreover, to investigate its effect on serum antioxidant activity. Twenty-five apparently healthy rabbits were divided into 5 equal groups, the 1 st group was the control and the 2 nd was the vaccinated group with 1 mL/rabbit S.C "Pasteurella multocida vaccine". The 3 rd group injected with 17.5 mg/rabbit of vitamin C and 1 mL/rabbit S.C "Pasteurella multocida vaccine" while, the 4 th group was given 1 mL S.C/rabbit Pasteurella multocida vaccine and 2.5 mg/kg BW tulathromycin. The 5 th group was treated S.C with 17.5 mg/rabbit vitamin C, 1 mL Pasteurella multocida vaccine and 2.5 mg/kg BW tulathromycin. The results showed a significant inhibition of lymphocyte transformation at 3 rd day, phagocytic activity and lysozyme activity at 1 st , 2 nd and 3 rd day of vaccination in the 4 th group. Moreover, its total globulin level was significantly depressed at the 7 th and 14 th day with a depression of antibody titre against pasteurella till the 3 rd week post vaccination. Comet results revealed a significant increase of DNA damage % on the 3 rd and 7 th days post vaccination. DNA fragmentation of neutrophil was transiently occurred in the 3 rd and 7 th days post treatment. It was concluded that, Tulathromycin has a transient immunosuppressive and genotoxic effect, therefore it should be administered in a combination with Vit C to overcome its side effects.

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