Toxicity Evaluation of in vitro Cultures of Freshwater Cyanobacterium Microcystis aeruginosa:Ⅰ.Hepatotoxic and Histopathological Effects in Rats

Laboratory cultures of freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa PCC 7806 was cvaluated for its hepatotoxic effects in rats. The lyophilized cell extract injected intraperitoneally at 1 and 2 LD50 (15.8 and 31.6 mg/kg, respectively) produced significant increase in liver-specific enzymes viz. plasma alkaline phosphatase,γ-glutamyl transferase, lactate dehydrogenase with a concomitant decrease in hepatic glutamic pyruvic transaminase. A corresponding increase in liver body weight index and histopathological changes in liver (degeneration of hepatocytes, congestion and hemorrhage etc.) are indicative of a dose and time dependent hepatotoxic nature of the algal extract

Effect of Pre-treatment of α-Ketoglutarate on Cyanide-induced Toxicity and Alterations in Various Physiological Variables in Rodents

Objective To investigate the effects of pre-treatment of α-ketoglutarate （α-KG） on cyanide-induced lethality and changes in various physiological parameters in rodents. Methods The LD50 of potassium cyanide （KCN） given orally （po）, intraperitoneally （ip）, subcutaneously （sc） or intravenously （iv） was determined in male mice, in the presence or absence α-KG given po, ip or iv. α-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index （PI） was calculated as the ratio of LD50 of KCN in the presence of α-KG （protected animals） and LD50 of KCN in the absence of α-KG （unprotected animals）. In a separate experiment, several physiological variables viz. mean arterial pressure （MAP）, heart rate （HR）, respiratory rate （RR）, neuromuscular transmission （NMT） and rectal temperature （RT） were measured in anesthetized female rats pre-treated （-10 rain） with po （2.0 g/kg） or iv （0.125 g/kg） α-KG and then administered sub-lethal （0.75 LD50） or lethal （2.0, 4.0 or 8.0 LD50） doses of KCN （po）. Results PI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with α-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg α-KG given ip （-10 min）, respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg α-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg α-KG given po at -10, -20 or -40 rain, respectively. No appreciable protection was observed when lower doses of α-KG （ip or po） challenged KCN given by sc route. Pre-treatment of iv or po administration of α-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of α-KG （po; 2.0 g/kg）. However, no protection was observed on NMT. Protective efficacy of α-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN. Decrease in MAP and NMT caused by 2.0 LD50 KCN （po） was resolved by iv administration of α-KG Conclusions Cyanide antagonism by α-KG is best exhibited when both α-KG and KCN are given by po route. The protective effect of α-KG on cyanide-induced changes in several physiological parameters also indicates a promising role of α-KG as an alternative cyanide antidote.

Cyanide Intoxication in Mice Through Different Routes and its Prophylaxis by α-Ketoglutarate

Antagonising effects of α-ketoglutarate (α-KG) could be attributed to complexing of the reactive nucleophile (CN-) to form cyanohydrin in cyanide intoxication. However, an enormous protection obtained could not be delineated on account of possible in situ binding of α-KG given intraperitoneally (i.p.) in mice to cyanide administered through the same route. The present study was designed to see the efficacy of a-KG alone or in combination with sodium nitrite (SN) and/or sodium thiosulfate (STS) in male mice exposed to cyanide administered through subcutaneous (s.c.) or inhalation route. A technique for generation of hydrogen cyanide (HCN) is also discussed. On the basis of protection index (PI), defined here as the LD50 of cyanide in protected mice/LD50 of cyanide in unprotected mice and survival time, STS + α-KG regimen was equipotent to the conventional SN + STS regimen. This is further substantiated by effect of α-KG in reducing plasma cyanide levels. The efficacy of α-KG remains undeterred irrespective of the route of cyanide intoxication, while the magnitude of protection varies.

Acute Toxicity of Methyl Isocyanate in Mammals. Ⅳ Biochemical and Hematological Changes in Rabbits

Subcutaneous administration of methyl isocyanate (MIC) in 0.5 LDso and 1.0 LD50 to female rabbits resulted in significant increases of hemoglobin concentration, hematocrit and leukocyte count in blood, as well as plasma total proteins, urea and cholesterol. A significant decrease in plasma albumin level was only observed in the 1.0 LD50 group. Urine of MIC intoxicated animals showed presence of protein, bilirubin, elevated urea and urobilinogen, while urine volume was reduced. The hematological and biochemical changes induced by MIC are perhaps the result of fluid loss from the vascular compartment as evidenced by the histopathological observations. This study further substantiates the view that acute toxicity of MIC is mediated in vivo by its effects on vascular beds.