Comparative Study of the Possible Protective Effects of Cinnamic Acid and Cinnamaldehyde on Cisplatin-Induced Nephrotoxicity in Rats

Abstract

This study aimed to assess the protective effect of cinnamic acid (CA) and cinnamaldehyde (CD) against cisplatin-induced nephrotoxicity. A single dose of cisplatin (5 mg/kg), injected intraperitoneally to male rats, caused significant increases in serum urea, creatinine levels, and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum albumin, reduced glutathione, and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) of kidney as compared with the control group. On the other hand, administration of CA (50 mg/kg, p.o.) or CD (40 mg/kg, p.o.) for 7 days before cisplatin ameliorated the cisplatin-induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress parameters. Furthermore, they reduced the histopathological changes induced by cisplatin. In conclusion, CA and CD showed protective effects against cisplatin-induced nephrotoxicity where CD was more effective than CA; affects that might be attributed to their antioxidant activities.

Cinnamic Acid and Cinnamaldehyde Ameliorate Cisplatin-Induced Splenotoxicity in Rats

“…Results in the present research disclosed that pretreatment with CA or CD significantly increased Hb concentration, TLC, and neutrophils as well as CAT activity and decreased lymphocytes and MDA splenic content, suggesting that their protective effects were related to antioxidative properties as compared to the CP‐treated group. A previous study demonstrated that CA or CD had protective effects against CP‐induced nephrotoxicity . Moreover, this study showed that CA or CD decreased TNF‐α splenic content; results which were in agreement with Song et al who revealed that CA and CD had a cardioprotective effect in a rat model of isoproterenol‐induced acute myocardial ischemia through their anti‐inflammatory and antioxidant properties.…”

Protective effect of aqueous extract of Lophira lanceolata leaf against cisplatin-induced hepatorenal injuries and dyslipidemia in Wistar rats

“…Creatinine is a non-protein nitrogenous substance formed from creatine and phosphocreatine during muscle metabolism but excreted by glomerular filtration. Just like urea, the rate of excretion of creatinine is influenced by glomerular filtration rate (GFR), so any abnormality that decreases GFR will result in an increased serum creatinine [21,22]. The significant increase in urea and creatinine levels after exposure of rats to cisplatin may be an indication of kidney impairments, due to the adverse effect of this drug.…”

“…The capacity of this plant extract to decrease urea and creatinine levels in rats may be attributed to its ability to protect the nephrons and increase GFR, as a result of its phytochemicals [21]. Previous studies have shown that certain plant extracts have protective effects against cisplatin-induced kidney injuries in animals by reduction of urea and creatinine levels [1,20,22]. The liver plays a major role in controlling plasma levels of cholesterol, thus when there is drug-induced liver impairments, there will be elevated levels of serum total cholesterol (TC) and LDL-cholesterol [17].…”

Superoxide Anion Production and Expression of gp91phoxand p47phoxAre Increased in Glomeruli and Proximal Tubules of Cisplatin‐Treated Rats

“…Currently, little is known about the mechanism involved in ROS generation; however, Marullo et al [31] showed that CP-induced intracellular ROS levels, as a consequence of its direct effect on mitochondrial DNA that leads to decreased synthesis of electron transport chain proteins and impairment of mitochondrial redox status, DNA integrity and bioenergetic functionality [31]. CP also induces a reduction in the activity of antioxidant enzymes [5][6][7]9] in kidney. Several studies have shown that a single dose of CP (7.5 mg/kg) induces acute renal failure in rats, characterized by high levels of plasma creatinine and BUN; these data were confirmed in our CP-treated rats.…”

“…Kuhlmann et al reported that the CP concentration in tubular epithelial cells is approximately five times higher than in plasma due to peritubular absorption . Several authors have described that oxidative/nitrosative stress and a decrease of antioxidant defense [‐; ] are involved in the development of CP‐induced renal damage. Davis et al found that CP also induces the production of reactive oxygen species (ROS) ; particularly superoxide anion (O 2 • ¯) [;], hydrogen peroxide (H 2 O 2 ) , and hydroxyl radical ( • OH) .…”