Hesperetin Protects Against Lead-induced Liver, Kidney And Testis Toxicity In Rats

Objective：The aim of this study was to investigate the possible protective role ofhesperetin on lead-induced toxicity in the liver, kidney and testicular of rats.Methods：24adult male Sprague-Dawley rats were randomly divided into fourgroups,6rats in each.(1) Control group, the rats received lead-free water and distilledwater (contain0.1%Tween-80) by oral gavage daily during the course of theexperiment;(2) hesperetin-treated group, animals received hesperetin at a dose of50mg/kg/day and distilled water daily by oral gavage;(3) lead-treated group, the ratsreceived an aqueous solution of lead acetate (Pb(CH3COO)2) at a concentration of500mg Pb/L as the only drinking fluid and distilled water (contain0.1%Tween-80) by oralgavage daily during the course of the experiment;(4) lead+hesperetin-treated group,animals received an aqueous solution of lead acetate (500mg Pb/L in drinking water)and received hesperetin at a dose of50mg/kg/day and distilled water daily by oralgavage. The experiment lasted for8weeks. At the end of experiment period, Rats wereanesthetized with ether. Blood samples were collected from all animals. The red bloodcell (RBC) count and the haemoglobin (Hb) concentration were determined usinganticoagulant blood. The serum obtained from no-anticoagulant blood aftercentrifugation was used for various serum biochemical assays. After blood sampleswere collected, all animals were sacrificed, the liver, kidney and testicular wereremoved, weighted and washed using chilled saline solution. Tissue was minced andhomogenized (10%, w/v) in appropriate buffer (PBS, pH7.4) and centrifuged. Theresulting clear supernatant was used for various enzymatic and non enzymaticbiochemical assays. A portion of the organs were fixed in10%formalin solution andused for pathological studies.Results:(1) The results showed that Lead has no significant effect on organcoefficient of rat liver, kidney and testicular. Lead causes a significant reduction in RBC count and count of Hb (P<0.05). Hesperetin has no significant effect on the red bloodcell count and hemoglobin content. Compared with the lead-treated groups, Hesperetincan increase the levels of RBC and Hb in blood of rat increased significantly (P<0.05).(2) Lead can cause liver damage. A very significant increase in the level of ALTand AST in the serum of lead-treated rats was observed when compared with controls(P<0.01). A significant decrease in the level of GSH content and in the activities ofSOD, GPx, and CAT, as well as an increase in MDA content were observed inlead-treated rats (P<0.05or P<0.01). Lead can cause liver pathological damage. Itshowed abnormal liver damage structures, partial liver cell swelling, no clear outline ordisappeared. Hesperetin has no effect on these indicators. But hesperetin cansignificantly reduce ALT, AST activities (P<0.01), significantly decrease liver MDAcontent (P<0.05), significantly increase the GSH content and GPx, SOD, CAT activities(P<0.05) compared with lead-treated group. Hesperetin can restore the hepatocytes tonear normal structure.(3) Lead can cause kidney damage in rats. A significant increase in the level ofurea, uric acid and creatinine in the serum of lead-treated rats was observed whencompared with controls (P<0.01). Lead can decrease the level of GSH content and inthe activities of SOD, GPx, and CAT, as well as an increase in MDA contentsignificantly (P<0.05or P<0.01). Lead causes renal pathology, tubular degeneration,necrosis, and even some tubules disappear, some narrowing of the renal capsule cysts,some glomerular atrophy. Hesperetin has no effect on these indicators. But hesperetincan significantly reduce urea, uric acid and creatinine contents (P<0.05or P<0.01),significantly decrease liver MDA content (P<0.05), significantly increase the GSHcontent and GPx, SOD, CAT activities (P<0.05) compared with lead-treated group.Hesperetin can restore the renal to normal structure.(4) Lead can cause testicular damage in rats. The results showed that MDAcontent and GPx activity in rat testis following the lead exposure increased significantly(P<0.05), the contents of GSH and CAT activity in testis decreased significantly(P<0.05or P<0.01). Lead can cause a wide range of seminiferous epitheliumdegeneration, necrosis, reducing the number of sperm cells at all levels, the basalmembrane defects in spermatogenesis, song seminiferous tubules of normal structuredisappeared. Hesperetin alone did not induce any significant changes in biochemicalchemistry of testis tissue. Compared the hesperetin antagonistic groups with the poisoning groups, the levels of MDA and GPx in testis of rat decreased significantly(P<0.05), the content of GSH and the activity of CAT increased significantly (P<0.05).Hesperetin can make testicular cells returned to normal structures.Conclusion: Lead can cause liver, kidney and testicular damage in rats.It showed thatlipid peroxidation and pathological damage. Hesperetin has a protective effect againstthis damage.