57 ± 6.1 mg/dL) with approx. 47% decrease, HDL (11.86 ± 2.4) with 45% find protocol increase and LDL (16.07 ± 8.6 mg/dL) with approx. 70% decrease over acetaminophen treated group and being comparable with the group treated with silymarin. Tinospora sinensis had specific effect on improvements in SGPT (176.60 ± 4.4 U/mL), ALP (22.13 ± 6.5 U/mL) with 58% decrease, VLDL (16.43 ± 2.6 mg/dL) and Triglyceride levels (82.15 ± 13 mg/dL) with 40% decrease when compared with acetaminophen treated group. It may be noted that the levels of VLDL and triglycerides in Tinospora sinensis treated group are found to be statistically insignificant when compared to silymarin treated

group, and hence are comparable to positive control. Neem guduchi was found to have specific effect on SGOT (147.43 ± 18.9) and bilirubin (1.05 ± 0.1) levels. The differential hepatoprotective effects of guduchi satwa prepared from these three Tinospora species are also evident from liver histology ( Fig. 1 a–f). The liver histology of the animals treated with T. cordifolia satwa exhibit improvements over acetaminophen treated group ( Fig. 1d) but with intermittently swollen centrilobular hepatocytes which are more prone to ischemic injury while periportal hepatocytes appear normal. The liver histology of the group treated with T. sinensis SB203580 research buy exhibits near normal histology ( Fig. 1e) with prominent

hepato-regeneration as evident from distribution of normal hepatocytes among degenerating swollen hepatocytes. This group also shows normal periportal hepatocytes. The liver histology of Neem guduchi satwa treated group ( Fig. 1f) is strikingly normal without any histologically detectable anomalies. The liver disorders are treated with an aim to prevent degeneration of hepatocytes and consequent metabolic derailments and to promote regeneration

of hepatocytes.3 Overdose of acetaminophen is known to have hepatotoxic effects which is reflected at the biochemical as well as histological level in the form of altered liver function tests and mild to severe alterations in the histological architecture already of hepatocytes. Tinospora is known to exhibit potent hepatoprotective and immunomodulatory activities. 19, 20, 21 and 22 The majority of studies on hepatic injury are found to be based on acute dosing of hepatotoxicant 23, 24, 25 and 26 and indicating the effect of Tinospora or other phytomedicines in alleviating hepatic injury. It is also known that the repeated dosing of acetaminophen, even for four days in male Sprague–Dawley rats leads to development of physiological adaptation to overdose of acetaminophen. 27 Hence care must be taken to design the animal experiments when considering acetaminophen as heptotoxicant, in order to avoid the dosage levels leading to development of physiological adaptation which may be mistaken as a hepatoprotective effect of the agent under investigation.