Abstract
BackgroundCisplatin is widely used chemotherapeutic agent for cancer treatment with limited uses due to its neurotoxic side effect. The aim of this study was to determine the potential preventive effects of rutin on the brain of cisplatin- neurotoxic rat model.MethodsForty rats were divided into four groups. Group-1 (control group) was intra-peritoneal (IP) injected with 2.5 ml/kg saline. Group-2 (rutin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days. Group-3 (cisplatin group) was IP received 5 mg/kg cisplatin single dose. Group-4 (rutin and cisplatin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days with a single dose of 5 mg/kg cisplatin IP on day ten. Brain tissues from frontal cortex was used to extract RNA, the gene expression levels of paraoxonase-1 (PON-1), PON-2, PON-3, peroxisome proliferator-activated receptor delta (PPAR-δ), and glutathione peroxidase (GPx) was investigated by Real-time PCR.ResultsCisplatin significantly decreased the expression levels of PON-1, PON-3, PPAR-δ and GPX whereas significantly increased PON-2 expression levels. Co-administration of Rutin prevented the cisplatin-induced toxicity by restoring the alteration in the studied genes to normal values as in the control group.ConclusionThis study showed that Rutin has neuroprotective effect and reduces cisplatin- neurotoxicity with possible mechanism via the antioxidant pathway.
Highlights
Cisplatin is widely used chemotherapeutic agent for cancer treatment with limited uses due to its neurotoxic side effect
Cisplatin causes cell-cycle arrest leading to apoptosis [4], but the core mechanism is its ability to covalently bind to Deoxynucleic acid (DNA) and to a broad range of essential Ribonucleic acid (RNA) molecules
40 rats were randomly divided into four groups and subjected to treatment as follows: Group-1 was IP injected with 2.5 ml/kg saline; Group-2 was orally administrated 30 mg/kg rutin for 14 days; Group-3 was IP injected with 5 mg/kg cisplatin single dose [43, 44] and Group-4 orally administrated 30 mg/kg rutin dissolved in water for 14 days with a single dose of 5 mg/kg cisplatin IP on the day ten
Summary
Cisplatin is widely used chemotherapeutic agent for cancer treatment with limited uses due to its neurotoxic side effect. The aim of this study was to determine the potential preventive effects of rutin on the brain of cisplatin- neurotoxic rat model. Platinum-based compounds, such as cisplatin, are part of standard treatment for various cancers [1]. Recent near atomic resolution study showed that cisplatin interacts with various RNA sites in the ribosome [5]. Cisplatin-related side effects (ototoxicity, nephrotoxicity, neurotoxicity and cerebral disorders) limits its clinical use at the desired dosage [6, 7]. Several studied have investigated the mechanisms of cisplatin toxicity but the Almutairi et al BMC Complementary and Alternative Medicine (2017) 17:472
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