| Objectives To observe the toxicity and reversibility by Rhubarb Water Decoction(RWD)and Rheum Total anthraquinone(RAT)in rats renal.Determined whether RTA is the toxic effects of the main parts of RWD.To guide medication safety.Methods Ninety Sprague-Dawley rats(8-week-old)were randomly divided into three groups.,which were normal control group(NC), RWD water decoction group(RWD) rheum RTA group(RAT), 30 in each group.The rats were given 2g/kg RWD and 73mg/kg RAT by gastric administration for 60 days.And then observe general state of the rats, after the last administration 24 h, withdrawal 30 days, 60 days, rats in each group were killed 1/3.Both kidneys were weighed to calculate the kidney organ index,and pathological examination were made by HE staining. Content changes of serum creatinine(SCr), blood urea nitrogen(BUN), β2-microglobulin(β2-MG)and urin β2-microglobulin(β2-MG) detected by biochemical.immunohistochemistry The protein expressions of Bcl-2 and Bax were detected by immunohistochemistry and Western blot.The genes expression of Bcl-2 and Bax were detected by RT-PCR.Results 1 General state:Administered on day 1 of each treatment group rats stools, soft stools, stool color dark brown;Urine of RAT group rat was brown. And RWD group was light red, and then turn into dark red after five days.In RTA group administered on day 15, and RWD group on day 30,rats were became fur cleanliness, reduced activity, poor spirit. Dorsal hair dyed red was also visibled in RTA group.And rats became worse until 60 d.RWD group was slightly better than the RTA group and no dorsal hair dyed red. In RWD group,the symptoms improve in withdrawal 10 d,improve fur finish, increased activity, increased food intake, and RTA group improve in withdrowal 30 d.In withdrawal 60 d, no difference was found in each group compared the NC group. 2 Effect in body weight: 1) male:From administered 42 d to withdrawal 28 d, compared with NC group,RWD group were significant weight loss(P<0.05 or P<0.01). From administered 35 d to withdrawal 28 d,compared with NC group,RTA group were significant weight loss(P<0.05 or P<0.01). Body weight of rats in each group, from withdrawal 35 d to withdrawal 60 d, the difference was not statistically significant compared with NC group(P>0.05). 2) female:From administered 28 d to withdrawal 35 d, compared with NC group,RWD group were significant weight loss(P<0.05 or P<0.01). From administered 21 d to withdrawal 35 d,compared with NC group,RTA group were significant weight loss(P<0.05 or P<0.01). Body weight of rats in each group, from withdrawal 42 d to withdrawal 60 d,the difference was not statistically significant compared with NC group(P>0.05). 3 Effect of kidney index:RWD group and RTA group administered 60 days kidney index were significantly higher than NC group(P<0.05 or P<0.01),and withdrawal 30 d, 60 d were no significant difference(P>0.05). 4 Effect of SCr, BUN, β2-MG in serum and β2-MG in urine: Administration of 60 d, RWD group and RTA group BUN was significantly higher than NC group(P<0.01).SCr and β2-MG content against normal group showed no significant difference(P>0.05).Withdrawal 30 d,60d, BUN, SCr, β2-MG content with NC group, the difference was not statistically significant(P>0.05). RWD group administered 60 days and RTA group urine β2-MG were significantly higher than NC group.Withdrawal 30 d,60d, urine β2-MG content with NC group, the difference was not statistically significant(P>0.05). 5 Effect on rats renal tissue structure:In administered. 60 d,compared with NC group, RWD anthraquinone group and total group renal proximal tubule epithelial cells swelling degeneration, renal tubular luminal narrowing, some epithelial cell shedding appeared empty, RTA group tubular epithelial cells appear dark brown unknown particles and dark brown particles increased with the severity. In withdrawal 30 d, compared with NC group, RWD group had no significant pathological changes in the kidneys, RTA group had mitigation,but the brown particle deposition were still visibled.In withdrawal 60 d, compared with NC group, RWD group and RTA group had no significant pathological changes in the kidneys,and the brown particle deposition were still visibled in RTA group. 6 Effect on protein and genes expression of Bcl-2, Bax: The protein and genes expression of Bcl-2 in RWD group and RTA group were significantly lower than NC group after adminstration 60d(P< 0.05 or P< 0.01), there were no statistical significance after withdrawal 30 d or 60d(P>0.05). The protein and genes expression of Bax in RTA group were significantly higher than NC group after adminstration 60d(P< 0.05). The protein and genes expression of Bax in RWD group adminstration 60 d,withdrawal 30 d, 60 d and RTA group withdrawal 30 d, 60 d were no statistical significance(P>0.05). The ratio of Bcl-2/Bax in protein and genes about RWD group and RTA group were significantly lower than NC group after adminstration 60d(P< 0.01),there were no statistical significance after withdrawal 30 d or 60d(P>0.05)Conclusions Rats renal function and structure will have a certain effect damage when RWD and RTA continuous used in two month.Speculated RTA may RWD major toxic components. And such damage is reversible... |
