Metallothionein Induced Mice Liver And Kidney Injury In Rats Of Combined Exposure Of The Nickel-chromium

Objectives：To study the damage effect induced by combining exposure to toxicants of nickeland hexavalent chromium in mice’s liver and kidney, and the protection effect andmechanism of metallothionein (MT).Methods：80Kunming (KM) mice, with female and male in half, were randomly dividedinto eight groups: low dose of nickel-chromium exposed group, medium and highdoses exposed groups, nickel-chromium exposed groups with low, medium, high doseof MT treated groups, MT group, control group. For the exposured groups, mice weregiven (Ni1.0, Cr0.5mg/kg),(Ni1.5, the Cr1.0mg/kg),(Ni3.0of Cr2.0inmg/kg) dose by gavage for10days, followed by normal saline for10days, respectively.As to the protection groups, different level doses were administered the same as theexposed groups, followed by5.0mg/kg-based MT for10days by gavage. MT groupwas given the same normal saline amount to the MT protection groups by gavage,followed by5.0mg/kg-based MT by gavage for10days. The normal control groupswas given normal saline once per day for20days agavaged at0.1mL/10g.bw in eachgroup. Blood sampling was taken after16hours’ none of eating by ethyl etheranesthesia at the end of the experiment. The animals were susequently cervicaldislocated and killed, at the same time, the liver and kidney were taken out andcalculated the organ coefficient. Routine pathological sections was taken to detectmorphological changes, followed by HE staining of liver and kidney. Indicators ofliver function such as of AST, ALT and GGT, total protein, albumin, total bile acidcontent and renal function such as BUN, CRE and K~+、Na~+、Cl~-content were detectedby clinical biochemistry automatic detector. Kidney liver tissue homogenate SOD,GSH-PX activity, MDA and GSH content was determined by using a classical kit.Results:1. Compared with control group and MT group, the body weight of mice of highdose group was decreased, while the liver and kidney organ coefficient increased(P<0.05); With MT protection, the mice liver and kidney organ coefficient in both medium and in high dose group were lower than that of exposure group (P <0.05);weight regain of MT protection group was not obvious (P>0.05), compared to thesame dose exposure group.2. Liver, kidney pathology observation:Liver tissue: whether low dose, medium groups, or high ones, liver cells varyeddegrees of edema, necrosis, cytoplasmic loose nucleus missing, sinusoidal networkstructure between the cells disappear, accompanied by a large number ofinflammatory cell infiltration, and aggravated lesions increased with dose of CHP;With MT protection, changes were seen that liver cells in all exposed groupsimproved in degrees, inflammatory infiltration, hepatocyte edema almost disappeared,cell necrosis and necrosis decreased, and that sinusoidal reticular somewhat recovered,in which MT of low dose group liver tissue recovery more obviously.Renal tissue: Most renal proximal tubule coagulately necrotized in both high andmedium exposure groups, of which medulla small pipe necrotized more common,other pathological changes were seen as dense granules, moderate to severehyperplasi in mesangial cells, edema, water degeneration; renal tubular damage,bleeding lesions, and so on. While as to low-dose exposure group, less pathologicalchanges were taken place; With MT protection, degeneration and necrosissignificantly reduced in renal tubular epithelial cell, with mesangial area restoring,other pathological changes such as water variability, cell tubular disappeared; nuclearnecrosis, hemorrhage and other diseases significantly improved.3. AST, ALT, and GGT levels of mice serum in all exposed groups of werehigher than that of control group and MT group(P<0.05); With MT protection, AST,ALT and GGT levels were lower than that of toxicants exposure group (P<0.05),showing a recovering trend; restoration of AST, ALT and GGT in both low andmedium dose groups were better than the high group (P<0.05).4. Serum total protein content of each exposure group were lower than thecontrol group and MT group (P<0.05). Albumin concentration in both medium andhigh dose group, and total bile acid content of high-dose group were lower than thecontrol group (P<0.05); With MT protection, total protein, albumin were higher thanthe same dose exposure group (P <0.05), while as total bile acid content was lower,showing a recovering trend.5. The contents of serum K+, BUN, of CRE in exposed groups were higher thanthat of control group and MT group, while as Cl-concentration was lower than the control group and MT group (P<0.05); the Na~+concentration of serum in high dosegroup was lower than the control group and MT group (P<0.05); With MT protection,K~+, BUN, CRE levels in blood were lower than the same dose group (P<0.05),showing a recoving trend.6. The MDA content of both mice liver and kidney tissure in each exposuregroup were higher than that of control group and MT group, while the content of GSHand activities of SOD, GSH-Px were lower than the control group and MT group. Andwith the dose of toxicant exposure increasing, content of MDA increased, comparedto that of GSH, SOD, GSH-Px decreased, which shew a dose-response relationship(P<0.05); With MT protection, the MDA contents of both mice liver and kidneytissure was lower than the same doses’ toxicants exposure group (P<0.05), while thecontents of GSH and activities of SOD, GSH-Px were higher (P<0.05), which wasshowing a recovering trend. However, the activities of SOD, GSH-Px recoveringtrend in both high and medium dose group were slower than low dose group (P<0.05).Conclusions:1. Combined exposure to different doses of bivalent nickel, hexavalentchromium led to functional injuries in mice liver and kidney, and injuries increasedwith the combined doses increasing.2. The metallothionein(MT) palyed a protective role in liver and kidney functioninjuries induced by combined nickel-chromium exposure, and protective effect wasmore obvious in low doses of combined exposure group, and the protectionmechanisms had a relationship with the anti-oxidative effect.