Study on synergistic effect of Qingkailing Injection and Shengmai Injection on organ injury in endotoxemia rats / 中国中药杂志

As a dangerous disease with rapid progression, endotoxemia is easy to induce the damage to multiple organs. However, its specific and efficient treatment methods are still lacking at present. Both Qingkailing Injection(QKLI) and Shengmai Injection(SMI) have been proved effective in anti-inflammation, anti-endotoxin and organ protection. In this study, carrageenan and endotoxin were injected successively into rats to establish an endotoxemia model. Different doses of QKLI and SMI were administered to the endotoxemia rats by intraperitoneal injection separately or in combination. Then the count of white blood cells, the number of platelets, the content of cytokines, biochemical indexes, organ coefficient and pathological changes of main organs in the rats were detected. The results showed that the rats in the model group had obvious symptoms of endotoxemia, i.e., leucopenia, thrombocytopenia, increase in cytokines(IL-6 and TNF-α) and biochemical indexes of liver and kidney function as well as pathological damage to liver, kidney and lung. QKLI alone can alleviate the above symptoms of endotoxemia and the organ injury. SMI alone is less effective in improving disseminated intravascular coagulation(DIC) and cytokine secretion complicated with endotoxemia, but capable of reducing the inflammation degree of the lung, liver and kidney. The combination of QKLI and SMI remarkably increased the number of platelets in the peripheral blood, improved the liver and kidney function and reduced inflammatory factors, with lung, liver, kidney and other organ structures protected well. Moreover, the improvement effect of the combination of QKLI and SMI was stronger than those of the two injections alone at fixed doses, indicative of a synergistic effect.

Protective effect of dexmedetomidine against organ dysfunction in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats

Dexmedetomidine (DEX), a selective agonist of α2-adrenergic receptors, has anti-inflammation properties and potential beneficial effects against trauma, shock, or infection. Therefore, this study aimed to investigate whether DEX might protect against multiple-organ dysfunction in a two-hit model of hemorrhage/resuscitation (HS) and subsequent endotoxemia. Eighty Wistar rats were randomized into four groups: NS (normal saline), HS/L (HS plus lipopolysaccharide), HS/L+D (HS/L plus dexmedetomidine), and HS/L+D+Y (HS/L+D plus yohimbine). Six hours after resuscitation, blood gas (PaO2) and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), creatinine (Cr), TNF-α, IL-β, IL-6, IL-8, IL-10, and nitric oxide (NO) were measured. The histopathology was assayed by staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) were assayed. The PaO2 levels in HS/L rats were lower whereas the ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, IL-10, and NO levels were higher compared to the control group. The HS/L+D increased PaO2 and further increased IL-10 and decreased ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, and NO levels of the HS/L groups. In addition, the MDA in the HS/L groups increased whereas SOD activity decreased compared to the control group. Moreover, the HO-1 expression levels were increased by DEX administration in lung, liver, and kidney tissues. Lungs, livers, and kidneys of the HS/L group displayed significant damage, but such damage was attenuated in the HS/L+D group. All of the above-mentioned effects of DEX were partly reversed by yohimbine. DEX reduced multiple organ injury caused by HS/L in rats, which may be mediated, at least in part, by α2-adrenergic receptors.

Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats

Endotoxemia caused by lipopolysaccharide [LPS] produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone [TQ], the main constituent of Nigella saliva seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione [GSH] and significantly increased the level of malondialdehyde [MDA] and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha [TNF-alpha] and bilirubin levels and the activities of alkaline phosphatase [ALP] and gamma-glutamyl transferase [gamma-GT] enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and decreases in the levels of MDA and caspase-3 activity in the liver with reduction of serum TNF-alpha, serum total bilirubin and the actvities of ALP and gamma-GTenzymes. Histopathological examination revealed that TQ administration improved LPS-induced pathological abnormalities in liver tissues. The present study conclude that TQ reduced acute endoxemia-induced liver dysfunction at least in part by its anti-inflammatory, antiapoptotic and antioxidant activities

insight into the possible protective effect of pyrrolidine dithiocarbamate against lipopolysaccharide- induced oxidative stress and acute hepatic injury in rats

Lipopolysaccharide [LPS] is a major cell wall molecule of Gram-negative bacteria known to stimulate the synthesis and secretion of several toxic metabolites, such as reactive oxygen species. In this study, the effect of pyrrolidine dithiocarbamate [PDTC], an antioxidant with nuclear factor- kappa B inhibitor activity, was evaluated in LPS-induced oxidative stress and acute hepatic injury in rats. Animals were pre-treated for 3 consecutive days with PDTC[200 mg/kg/day, i.p.] or saline and animals were then challenged with LPS[6 mg/kg, i.p.] or saline. Six hours after LPS injection, animals were decapitated and blood and liver samples were collected to assess the chosen biochemical parameters. Saline-pretreated animals challenged with LPS revealed extensive liver damage, as evidenced by increase in serum levels of alanine aminotransferase [ALT], aspirate aminotransferase [AST] and gamma glutamyl transferase [gamma -GT]. Also, LPS treatment resulted in significant increases in serum lactate dehydrogenase [LDH], tumor necrosis factor-alpha [TNF- alpha] and nitrite levels. Furthermore, LPS challenge caused oxidative stress as indicated by an increase in hepatic lipid peroxidation measured as thiobarbituric acid reactive substances [TBARS] and a decrease in hepatic reduced glutathione concentration [GSH] as well as decreased activities of superoxide dismutase [SOD] and [GSH] as well as decreased activities of superoxide dismutase [SOD] and catalase in hepatic tissues. The administration of PDTC prior to LPS challenge resulted in improved liver functions as evidenced by the decline in serum AST, ALT, gamma-GT levels and reduction in serum LDH, TNF- alpha and nitrite levels. Moreover, PDTC reduced the chosen lipid peroxidation marker, TBARS and increased GSH concentration, and SOD and catalase activities in hepatic tissues. These results indicate that PDTC may be a useful pharmacological agent in alleviating LPS-induced oxidative stress and acute hepatic injury

Combined Administration of Glutamine and Growth Hormone Synergistically Reduces Bacterial Translocation in Sepsis

We investigated the combined effect of glutamine (GLN) and growth hormone (GH) on bacterial translocation (BT) in sepsis. After single intraperitoneal injection of lipopolysaccharide (10 mg/kg), 48 rats were divided randomly into four groups of 12 animals each: the control group received chow orally; the GLN group received chow plus 10% GLN; GH group received chow plus GH; and the GLN/GH group received chow, 10% GLN, and GH. Twenty-four and 96 hr later, rats were sacrificed. Portal blood culture, bacterial colony counts of cultured mesenteric lymph nodes, mucosal thickness, malondialdehyde (MDA), and glutathione (GSH) levels in the gut mucosa were measured. There was no significant change of the rate of portal blood culture between all treatment groups at 24 and 96 hr. At 24 hr, the rats receiving combined treatment of GLN and GH showed lower bacterial colony counts and mucosal MDA levels than the control rats, and higher mucosal GSH levels than the control and GLN-treated rats. At 96 hr, rats treated with both GLN and GH exhibited lower bacterial colony counts and mucosal MDA levels, and higher mucosal thickness and GSH levels than control, GLN, or GH-treated rats. This study suggests that the combination of GLN and GH may synergistically reduce BT over time in sepsis.