Effects Of Dimethyl Sulfoxide On Zymosan-induced Systemic Inflammation And Multiple Organ Dysfunction

Objective: Previous studies have found that dimethyl sulfoxide(DMSO) can suppress ischemia and sepsis-induced expression of proinflammatory cyto-kines, and reduce the injury of important organ function. Purpose of this study: To study the protective effect and mechanism of DMSO on zymosan-induced systemic inflammation and multiple organ dysfunction.Methods:1 Groups and treatments: SD rats of clean-level, weight 180~220g, were randomly divided into 4 groups: group SS, Sham + saline group; group SD, Sham +DMSO group; group ZS, Zymosan + saline group; group ZD, Zymosan +DMSO group. Rats were given an IP injection of zymosan(750mg/kg, dis-solved in saline) in group ZD and group ZS, followed by subcutaneous injection of DMSO(3ml/kg, diluted in saline 1:2) and normal saline(3ml/kg) at 1h after zy-mosan administration. Group SS and group SD were treated as surgery and drug control. According to different observation time, each group was divided into three subgroups: 4h, 8h and 24 h after injury(n=10) for detection. In another set of experiments, group ZD and group ZS were randomly assigned and monitored for survival for 24 hours after zymosan administration.( =20)2 Measurements and methods: Mental state of rats was observed after zy-mosan administration, as well as the survival at 4, 8, 12, 18 and 24 h. The blood flow of liver, kidney and intestinal were monitored with laser-Doppler flowmeter at 4h, 8h and 24 h. The plasma levels of ALT, CR, the activity of DAO, tumor ne-crosis factor-α(TNF-α) and interleukin-6(IL-6) were also detected. The speci-mens of liver, kidney and intestine were harvested for evaluation of malondial-dehyde(MDA), myeloperoxidase(MPO) and determination of water content of those organs by dry/wet weight method. To observe the histomorphology changes of those organs under light microscope after HE staining.Results:1 Symptoms and survival: After zymosan administration, rats became le-thargic with ruffled fur, breathing difficulties, sleepiness, diarrhea, apastia, less activity and drink, body curled up, bloody discharge at the corner of the eye and mouth. 55% rats survived at 24h; After DMSO administration, the symptoms were significantly improved in rats, and 90% survived at 24 h, which was higher than that in ZS group.2 The blood flow of liver, kidney, intestinal: The blood flow of liver, kidney, intestinal in group ZS and group ZD were significantly lower than group SS and group SD(P<0.05) after zymosan administration. It was the lowest at 24 h which was respectively 47.42% and 61.59% of group ZS and group ZD in blood flow of intestinal. In liver and intestine, at 8h and 24 h, group ZD was significantly higher than group ZS(P<0.05), as well as 4h, 8h and 24 h in kidney.3 Tissue water content: The water content of kidney and intestinal in group ZS were significantly higher than group SS and group SD(P<0.05) at 4h after zymosan administration. The water content of kidney in group ZD was signifi-cantly higher than SS and group SD(P<0.05). The water content of intestinal in group ZD was lower compared with group ZS(P<0.05). At 8h and 24 h, the water content of liver, kidney and intestinal in group ZS and group ZD were signifi-cantly higher than group SS and group SD(P<0.05).It was significantly lower in group ZD compared with group ZS(P<0.05).4 The content of ALT, CR and the activity of DAO: The content of ALT, CR and the activity of DAO in group ZS and group ZD were significantly higher than group SS and group SD(P<0.05) after zymosan administration. The content of ALT and the activity of DAO in group ZD were significantly lower than group ZS at 8h and 24 h. The content of CR in group ZD was significantly lower than group ZS(P <0.05) at 24 h.5 Serum TNF-α and IL-6 content: The serum TNF-α and IL-6 content in group ZS and group ZD were significantly higher than group SS and group SD(P<0.05) after zymosan administration. The serum TNF-alpha was the highest at 4h and IL-6 was the highest at 24 h in group ZS and group ZD. The TNF-alpha and IL-6 content in group ZD were significantly lower than that in group ZS at each time point(P <0.05).6 The activity of MPO and the content of MDA in liver, kidney and intestin-al: The activity of MPO and the content of MDA in liver, kidney and intestinal in group ZS and group ZD were significantly higher than group SS and group SD(P<0.05) after zymosan administration. The content of MDA in liver and intestin-al in group ZD were significantly lower than group ZS at 8h and 24h(P<0.05), as well as in kidney at 4, 8h and 24h(P<0.05). There were no significantly differ-ence between the activity of MPO in group ZD and group ZS.7 Pathomorphology observation: At 24 h after zymosan administration, we could observe hepatic vascular congestion, cell swelling, patchy necrosis; renal interstitial edema, inflammatory cells infiltration, tubular epithelial cell swelling, necrosis; intestinal mucosal erosion, villous hyperemia, edema, and atrophy, in-flammatory cell infiltration, epithelial cell swelling, necrosis and shedding. The group ZD were significantly improved compared with group ZS, and no patho-logical changes in group SS and group SD.Conclusion:The rats with DMSO administration can significantly reduce systemic in-flammatory response and tissue edema induced by the zymosan, improve organ function and the survival in 24 h. Its mechanism may be related that DMSO can increase the organ blood flow, suppress proinflammatory cytokine levels and in-hibit peroxidation.