The First Year Research (Sri Ram Chandra University Chennai 2012-13)
The effect of long term, possible, toxicity potential of SAVLIV was determined by oral administration at doses of 250, 500 and 1000 mg/kg/day in male and female Wistar rats for a period of 90 days.
Mortality, body weight changes, abnormal clinical signs, feed intake, hematology, electrolytes, biochemistry, organ weight changes and pathology were evaluated. There was no treatment related death, remarkable body weight changes, clinical signs of toxicity, alterations in feed intake, gross pathological and organ weight changes observed in vehicle or SAVLIV treated animals.
No significant difference in haematological parameters and electrolytes were observed in SAVLIV administered rats.
A significant (p<0.05) difference in percentage of eosinophills was observed at high dose and satellite high dose treated animals compared to their respective controls, a significant (p<0.01) difference in percentage of reticulocyte was observed at mid dose compared to their respective control, however in both the cases the values were within the clinical range. No difference in other differential count parameters was observed in all the experimental groups.
Although a significant (p<0.05) elevation in bilirubin was observed in SAVLIV high dose - satellite group when compared to the respective control, however the values were within the clinical range of rats. No alterations in other biochemical parameters were observed in SAVLIV administered rats.
There were no treatment related gross pathological changes and histopathological findings observed in SAVLIV administered rats.
There were no treatment related delayed occurrence or persistent of toxicity were observed in satellite group during its recovery period.
Under the tested conditions, SAVLIV was found to be well tolerated up to 1000 mg/kg b.wt, when administered orally for a period of 90 days in rats.
Hence, No-Observed-Adverse-Effect-Level (NOAEL) is found to be greater than 1000 mg/kg/day when administered for a period of 90 days in rats.
The Second Year Research (Sri Ram Chandra University Chennai 2014-15)
In the final year of the project, the 28 and 90 day repeated oral toxicity of SAVLIV drops was investigated in experimental animals.
28-day repeated oral toxicity study of SAVILV was carried out following OECD test guideline 407 at three dose levels (250, 500 and 1000 mg/kg b.wt.). Administration of SAVLIV drops for a period of 28 days did not produce any changes in body weight, feed intake, water intake and gross or histological parameters when compared to the vehcile treated rats. A significant alteration in few hematological, electrolyte and biochemical parameters were observed at 1000mg/kg b.wt treated female rats. Based on the data, Low-Observed-Adverse-Effect-Level (LOAEL) of SAVILV was found to be 1000mg/kg/day and No-Observed-Adverse Effect-Level (NOAEL) of SAVILV was 500 mg/kg/day, when administered orally for a period of 28 days in rats.
90-day repeated oral toxicity was performed for SAVILV as per OECD test guideline 408 at three dose levels (125, 250 and 500 mg/kg b.wt). There were no changes in body weight, feed intake, water intake and gross or histological changes in the 90 day repeated oral toxicity study. Though a significant changes in hematology and biochemical parameters were observed at 500 mg/kg b.wt treated rats but they were within the clinical range of rats. Based on the data, Low-observed-Adverse-Effect-Level (LOAEL) of SAVILV was found to be 500 mg/kg/day and No-Observed-Adverse Effect-Level (NOAEL) of SAVILV was 250 mg/kg/day, when administered orally for a period of 90 days in rats.
In both 28 and 90 day repeated oral toxicity studies, no treatment related changes or delayed occurrence of toxicity signs were observed in SAVLIV treated animals during recovery period at 14th and 30th day respectively.
Further, hepatoprotective effect of SAVLIV was investigated using chemically (Paracetamol, Ethanol and CCl4) induced hepatotoxicity mice model. SAVLIV pretreatment at 25mg, 50mg and 100 mg/kg prevented the hepatotoxic damage induced by chemicals in dose dependent manner which was evidenced in reduced level of hepatobiliary enzymes. The results further confirm the hepatoprotective effect of SAVLIV. It is mainly due to the presence of high content of antioxidant rich ingredients especially total phenols, Vitamin C and citric acid in SAVLIV formulation.
In view of the above, SAVLIV can be developed as an effective therapeutic agent for drug/alcohol-induced liver disease in future.