L-arginine ameliorate acute ocular toxicity induced by cisplatin administration in rats: role of inducible nitric oxide synthase

Abstract

Cisplatin (CP) is a chemotherapeutic agent employed as a therapy for different solid tumors.  CP elicits many negative side effects including ocular toxicity. L-arginine able to increase the anti-inflammatory cytokine levels in the bloodstream.  This study aimed to evaluate the possible protective impact of L-arginine against ocular toxicity of cisplatin through its anti-inflammatory action.  Forty male rats were utilized in this experiment. The treatment protocol duration lasted for one week. The rats were divided randomly into four equal groups, as follows: the normal control group (G1) received a single intraperitoneal injection of normal saline, Cisplatin-administered group (G2) received single intraperitoneal injection of cisplatin in a dose (10 mg/kg body weight), Cisplatin + L-arginine-treated group (G3) received i.p. injection of cisplatin in a dose (10 mg/kg b.wt.) followed immediately by i.p. injection of L-arginine in a dose (10 mg/kg b.wt.), and  L-arginine-treated group (G4) received intraperitoneal injection of 10 mg/kg b.wt. L-arginine. The protective effect of L-arginine was assessed through histopathology and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) in ocular tissues.  Cisplatin-administered group revealed corneal neovascularization, stromal inflammatory infiltration, corneal epithelial hyperplasia, and endothelial degeneration. Sclera revealed vascular congestion and inflammatory infiltrates. There were congested blood vessels, apoptosis, and a decrease the ganglionic cells number in the retinal tissue. Ciliary body had epithelial necrosis, congestion, and hemorrhage. These pathological changes were attenuated to be mild in the cisplatin + L-arginine-treated group. The intensity of the immunohistochemical expression of iNOS appeared weak and significantly decreased in G3 compared to G2. The obtained data validate that Co-treatment of cisplatin with L-arginine cause a reduction in histopathological ocular damage through its anti-inflammatory effect.