The master’s thesis entitled “Evaluation of the Possible Protective Effect of Citronellol against Methotrexate-Induced Nephrotoxicity in Rats” was discussed for the researcher Dania Thaer Sabri and her supervisor Assistant Professor Dr. Mohammed Abdul-Hassan Jabarah, a faculty member of the College of Medicine / University of Baghdad, at the Pharmacology Department.
The study aimed to evaluate the possible protective effect of Citronellol against nephrotoxicity induced by Methotrexate in rats, and to investigate the mechanisms underlying Citronellol’s possible reno-protective effect.
The study included twenty-four adult male Wistar rats that were randomly allocated into four groups, consisting of six rats each, and they were treated as follows: Group I rats received 1 mL/kg corn oil orally for 14 consecutive days; Group II rats received 1 mL/kg corn oil orally for 14 consecutive days and a single intraperitoneal injection of 20 mg/kg Methotrexate on day 11; Group III rats received 100 mg/kg Citronellol orally for 14 consecutive days and a single intraperitoneal injection of 20 mg/kg Methotrexate on day 11; Group IV rats received 200 mg/kg Citronellol orally for 14 consecutive days and a single intraperitoneal injection of 20 mg/kg Methotrexate on day 11. After 24 hours from the final administration, the experimental rats were anesthetized and blood samples were collected for biochemical assays, then, the kidneys were surgically removed for biochemical and gene expression analyses, after which rats were sacrificed by exsanguination.
The results showed that pre-treatment with 100 or 200 mg/kg Citronellol significantly ameliorated renal damage biomarkers, including serum urea, serum creatinine and kidney injury molecule-1 in comparison with the Methotrexate group. In addition, pre-treatment with 100 or 200 mg/kg Citronellol significantly enhanced the levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, diminished renal malondialdehyde contents and attenuated inflammation via suppressing renal nuclear factor kappa B signaling and diminishing tumor necrosis factor-alpha gene expression, as compared with the Methotrexate group. Moreover, pre-treatment with 200 mg/kg Citronellol significantly reduced interleukin-1 beta gene expression when compared with the Methotrexate group.
The study recommended that further researches utilizing a larger scale of experimental animals and longer intervals are highly warranted, also, to evaluate the possible protective effect of Citronellol against other organ toxicities induced by Methotrexate, such as hepatotoxicity.
