ABSTRACT
Cisplatin is a major antineoplastic drug for the treatment of solid tumors. Nephrotoxicity is dose- limiting side effect associated with clinical use of cisplatin. The present study was executed to determine whether bartogenic acid containing fraction of Barringtonia racemosa fruits (BREAF) possesses a nephroprotective effect against cisplatin-induced nephrotoxicity in rats. Furthermore, the study was also aimed to explore the mechanisms underlying this effect of BREAF. The BREAF was orally administered at the doses of (2, 5 and 10 mg/kg) for five consecutive days following single dose administration of cisplatin (5 mg/kg, i.p.). Treatment of animals with cisplatin resulted into the significant body weight changes, oxidative stress, elevated levels of serum biomarkers and histological alterations in the kidney architecture. The BREAF administration reduced relative body weight and organ weight changes in cisplatin-treated rats. The BREAF exhibited nephroprotective effect through the significant reduction of cisplatin-induced rise in the serum creatinine, and blood urea nitrogen levels as well as renal levels of malondialdehyde (MDA) the makers of lipid peroxidation. Additionally, the treatment with BREAF resulted into the increased renal levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase activity. Histopathological examination established the nephroprotective effect of BREAF. In conclusion, the anti-oxidant, and anti-inflammatory effects of BREAF has important role underlying its nephroprotective effect.
ABSTRACT
Barringtonia racemosa (B. racemosa) is a tropical medicinal plant possessing interesting biological activities. B. racemosa fruits are traditionally used in India for the treatment of pain, inflammation, and rheumatic conditions. Earlier, we have reported anti-inflammatory activity of ethyl acetate fraction (BREAF) obtained from B. racemosa fruits in animal models of inflammation and delayed-type hypersensitivity. The present study aimed to assess the anti-nociceptive activity of BREAF. Acetic acid-induced writhing test, and hot plate and tail immersion tests were employed to study the effect of BREAF on peripheral and central pain mechanisms, respectively. The involvement of opioid system was confirmed through naloxone antagonism. Formalin induced pain test was performed to assess the effect of BREAF on neurogenic and inflammatory pain components. Capsaicin induced pain models were used to investigate the involvement of transient receptor potential vanilloid 1 receptor. The BREAF reduced writhing episodes and delayed the onset of acetic acid-induced writhings. The raised percentage maximum protective effects by BREAF in hot plate and tail immersion tests suggest the efficacy of BREAF in pain alleviation. A reversal of the analgesic effect of BREAF following naloxone treatment indicates the involvement of opioid receptors. The BREAF also inhibited inflammatory and neurogenic components of formalin-induced pain. The inhibition of capasaicin induced pain to some extent by the BREAF indicates the possibility of involvement of TRPV1 receptors. This study reinforces the traditional use of B. racemosa in the treatment of painful conditions. However, further studies are reasonable to explore the detailed mechanism(s) of the anti-nociceptive action of BREAF.