Biochemical and histologic study of lethal cisplatin nephrotoxicity prevention by mirtazapine.
BACKGROUND
Cisplatin is a platinum derivative frequently used in the chemotherapy of different solid tumors. This biochemical and histologic study investigated a possible protective effect of mirtazapine with regard to cisplatin-induced nephrotoxicity in the rat.


METHODS
The animals were divided into 4 groups: 15 mg/kg mirtazapine + 10 mg/kg cisplatin, 30 mg/kg mirtazapine + 10 mg/kg cisplatin, only 10 mg/kg cisplatin and negative control (healthy) group. During 14 days, the treatment and treated control group took drugs, while the healthy animals were given distilled water on the same schedule. All animals were sacrificed by high-dose anesthesia at the end of the 14 days of treatment; their kidneys were removed and subjected to histologic and biochemical study.


RESULTS
In both of the doses we used, mirtazapine decreased the levels of malondialdehyde, creatinine, blood urea nitrogen and myeloperoxidase activity when compared to cisplatin group. On the other hand, it increased total glutathione level in all doses. Slight histopathological findings were determined in mirtazapine groups when compared to cisplatin control group.


CONCLUSIONS
In the light of our results and literature knowledge, we can conclude that the protective effect of mirtazapine in cisplatin toxicity originates from its own antioxidant activity.
Department of Forensic Medicine, Faculty of Medicine, Ataturk University, Campus, 25240, Erzurum, Turkey.
Mustafa Talip
MT
Sener
Ebru
E
Sener
Adem
A
Tok
Beyzagul
B
Polat
Irfan
I
Cinar
Harun
H
Polat
Fatih
F
Akcay
Halis
H
Suleyman
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000929:Antidepressive Agents, Tricyclic; D000970:Antineoplastic Agents; D000975:Antioxidants; D008803:Mianserin; D008315:Malondialdehyde; D000078785:Mirtazapine; D003404:Creatinine; D009195:Peroxidase; D005978:Glutathione; D002945:Cisplatin