Life Science Journal 2013;10(1) http://www.lifesciencesite.com 2119 The Toxic Effect of Melamine on the Kidney of Male Rats as Revealed by Biochemical and Histopathological Investigations Haddad A. El Rabey *1 , Abdulbasit I. Al- Sieni 1 and Abdullah A. Majami 2 1 Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. 2 FDA, Jeddah, Saudi Arabia elrabey@hotmail.com Abstract: This study aimed to evaluate the toxic effect of four different melamine doses (5000, 10000, 15000 and 20000 ppm) supplemented orally in the diet for 28 days on male rats. The appearance, anatomy, serum electrolytes, kidney functions (creatinine, urea and uric acid), serum melamine concentration, total body weight, food intake, food efficiency ratio (FER), body weight gain (BWG), percentage of body weight gain (BWG %), water consumed and histopathological examinations of three organs (kidney, ureter and urinary bladder) were investigated. The melamine supplemented rats turned yellow and showed different degrees of toxicity, hypertrophy and congestion, particularly the kidneys and the ureters as a result of melamine toxicity. Serum Na and Cl levels were decreased, whereas serum K, P and Ca levels were increased compared to the negative control. Kidney functions showed elevation of the mean values of serum creatinine, urea and uric acid. The histopathological examination of the three organs under study showed adverse pathological signs according to the melamine dose. [Haddad A. El Rabey, Abdulbasit I. Al- Sieni and Abdullah A. Majami. The Toxic Effect of Melamine on the Kidney of Male Rats as Revealed by Biochemical and Histopathological Investigations. Life Sci J 2013;10(1):2119-2130]. (ISSN: 1097-8135). http://www.lifesciencesite.com . Keywords: electrolytes, melamine, creatinine, kidney, histopathology. 1. Introduction: Melamine, or 1,3,5-triazine-2,4,6-triamine, is a small, nitrogen-rich molecule. It was considered non-toxic based on early laboratory animal studies until significant morbidity and mortality related to crystalluria, nephrolithiasis and nephrotoxicity have resulted from pet food contamination (Bischoff, 2011). It is harmful if swallowed, inhaled or absorbed through the skin and chronic exposure may cause cancer or reproductive damage. It is eye, skin and respiratory irritant (Weise, 2007). Direct contact results in skin irritation and eye irritation, and inhalation causes respiratory tract irritation. Oral ingestion affects the digestive tract, presenting as nausea, vomiting, and diarrhea (Jeong et al., 2006). The mechanism of carcinogenesis was most likely secondary to epithelial hyperplasia caused by mechanical irritation (Hau et al., 2009). Melamine is minimally, if at all, metabolized in monogastrics, but could be partially metabolized in the rumen of cattle and small ruminants. Melamine does not accumulate over time in the animal body. Renal elimination of unchanged melamine is approximately 90% complete within 24 hours (Qin et al., 2010). The combination of melamine and cyanuric acid in diet does lead to acute renal failure in cats (Puschner et al., 2007) and rats (Dobson et al., 2008). Dalal and Goldfarb (2011) reviewed the toxicology, epidemiology, and pathology due to melamine contamination of foodstuffs due to melamine contamination only or in combination with cyanuric acid. In 2008, melamine contamination of baby milk-based products was detected in China. Chinese authorities detected melamine concentrations between 2.5 and 2563 ppm in 13 commercial brands of milk powder and trace contamination in nine others (Bhalla et al., 2009). Gonzalez et al. (2009) discovered renal failure in piglets in Spain between 2003 and 2006. They found that the kidneys contained melamine, cyanuric acid and relatively high concentrations of ammelide and ammeline. Lv et al. (2010) found that melamine concentrations in the kidney were higher than concentrations in the skeletal muscle or liver of lambs, and concentrations decreased below 20 ppb 4 days after cessation of exposure. Addition of cyanuric acid to the diet did not affect melamine deposition. On the other hand, Shen et al. (2010) stated that melamine is excreted by dairy cattle into milk, particularly in high-producing cattle, though milk yield and composition are otherwise unaffected. Melamine can be detected in milk within 8 hours of exposure and remains detectable until 4 days after cessation of exposure. Approximately 0.3% of a melamine dose was excreted in milk in dairy goats, and milk melamine concentrations remained above the level of concern (1.0 µg/mL) until 3 days after cessation of dosing (Baynes et al., 2010). Kim et al. (2010) using rat models, investigated the renal crystal formation following the