The effect of cerebrolysin on cisplatin induced optic nerve injury in rats

The Effect of Cerebrolysin on Cisplatin Induced Optic Nerve Injury in Rats Background and aim: Cisplatin is a platin derived, wide-spectrum anti-cancer drug which has been used in adult and child patients with various malignancies. Effective dose of cisplatin which has an anti-cancer effect in patients is also toxic to normal tissues. Optic neuropathy has been reported to be one of the most important toxic effects related to usage of the cisplatin and a known reason for cessation of the treatment. During the cisplatin treatment, reduced antioxidant levels and increased reactive oxygen radicals (ROR) along with intercellular damage due to lipid peroxidation were reported in the literature. According to data in the literature, antioxidants and neurotrophic agents may be useful in the treatment of cisplatin related optic neuropathy. In our study, we aim to research the protective effect of cerebrolysin which is mixture of amino acids and low molecular weight peptides extracted from swine brain on cisplatin related oxidative optic nerve injury owing to its potential neuroprotective and neurotrophic properties. There are studies in the literature that associate its neuroprotective and neurotrophic effects with antioxidant potency. On the brink of these findings, cerebrolysin may be helpful in the treatment of cisplatin induced oxidative optic nerve injury. To our knowledge, there is no clinic and preclinic research has been conducted in the literature concerning the effect of cerebrolysin on the cisplatin induced oxidative optic nerve injury so far. We aim to investigate the histopathologic and biochemical effects of cerebrolysin in rats with oxidative optic nerve injury induced by cisplatin. Materials and methods: Albino Wistar rats were divided into three groups as healthy (H), only cisplatin injected (2.5mg/kg) (CIS) and cisplatin plus cerebrolysin (2.5mg/kg and 2.5mL/kg respectively) injected (CCG). CCG (n=10) group received 2.5mL/kg dose of cerebrolysin solution preparation via intraperitoneal injection (IP). CIS (n=10) and H (n=10) groups received saline injection with the same dose and same route. One hour after the IP, CCG and CIS groups were further administered cisplatin with a dose of 2.5mg/kg via IP. Cisplatin and saline injections were repeated for 14 days with mentioned doses daily. After this period, all rats were killed using high dose of thiopental (50mg/kg) anesthesia and optic nerves were collected. Levels of malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), superoxide dismutase (SOD) with total antioxidant status (TAS) and total oxidant status were measured in the specimens. Tissues also underwent histopathological examination. Results: In biochemical analysis, MDA, MPO and TOS levels detected within the optic nerve tissue were significantly higher in CIS group compared to H and CCG groups (p<0,0001) whereas tGSH, SOD and TAS levels were significantly lower in CIS group compared to H and CCG groups (p<0,0001). Conclusion: Our results imply that cerebrolysin may be helpful in the treatment of cisplatin induced oxidative optic nerve injury. Keywords: Nerve, Optic Nerve Injury, Cerebrolysin, Oxidative Stress, Oxidant, Antioxidant