Background: The present study was undertaken to investigate protective activity of W. somnifera root extract (W.S.R.E.), cow urine (C.U.) and their combination against acetaminophen (APAP) induced toxicity in male mice. APAP also known as paracetamol, is a well-known drug used for its analgesic and antipyretic effects. However, outside of the therapeutic window, the toxicity may result. W.S. and C.U. are from indigenous sources of plant and animal origins, respectively with several therapeutic activities. 
 
Methods: Sixty adult swiss albino male mice were randomly divided into six groups, comprising of ten mice in each group. Group I (control group) received 2% gum acacia suspension for 14 days orally and on day 14, 0.9% NaCl (@300 mg/kg b.wt.) intraperitoneally was administered after 30 min of prior treatment of various agents. Group II, III, IV, V and VI received 2% gum acacia, silymarin (@25 mg/kg b.wt.), W.S.R.E. (@100 mg/kg b.wt.), C.U. (@7.8 mL/kg b.wt.) and W.S.R.E.&nbsp;(@100 mg/kg b.wt.) and C.U. (@7.8 mL/kg b.wt.) co-treatment orally for 14 days and on day 14, APAP (@300 mg/kg b.wt.) intraperitoneally was administered after 30 min of prior treatment of various agents as mentioned. On 15th day, the animals were sacrificed and samples were collected to study various hematobiochemical and growth related parameters. 
 
Result: The treatment of acetaminophen caused significant decrease in haemoglobin, total erythrocyte count whereas increase in total leucocyte and prothrombine time. There were significant (p&pound;0.05) decreases in plasma total protein, albumin and globulin values in group II (APAP), as compared to control (group I). Treatment with W.S. +C.U attenuates these alterations. W.S.R.E., C.U. and their combination pre-treatment mildly restored the changes to normal observed following APAP exposure in mice. However, the results of co-treatment group were more pronounced as compared to individual treatment groups. Thus, it was concluded that treatment with W.S.R.E. and C.U. curtailed the toxic effect of APAP, however, co-administration of both potentiated the protective effect.

Influence of Pre-treatment of Withania somnifera Root Extract and Cow Urine on Hemato-biochemical Parameters in Acetaminophen-induced Toxicity in Swiss Albino Male Mice

Background: Acetaminophen (APAP), a commonly used analgesic, causes acute kidney injury (AKI) in overdose although it is rare. Mitochondrial dysfunction plays a major role in the pathophysiology of renal damage, although the exact molecular mechanism is unknown. This study aimed to evaluate the potential therapeutic effect of cyclosporin A (CsA), a mitochondrial membrane permeability transition pore (MPTP) inhibitor, with N-acetylcysteine (NAC) in APAP-induced AKI.&nbsp; 
 
Methods: Male BALB/c mice were divided into control, APAP, APAP+NAC, APAP+CsA and APAP+NAC+CsA groups (n=6). A single dose of APAP (400 mg/kg) was administered intraperitoneally. All other treatments (1200 mg/kg NAC, 50 mg/kg CsA) were performed intraperitoneally 3 h after APAP administration. All animals were decapitated and blood samples and kidney tissue samples were collected for evaluation. Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured. The kidney tissue 8-hydroxy-deoxyguanosine (8-OHdG), cytochrome c (Cytc) and 3-nitrotyrosine (3-NT) levels and cytochrome c (Cytc) expressions were determined.&nbsp; 
 
Result: Increased Cr and BUN levels, histopathological examinations and expressions of 8-OHdG, 3-NT and Cytc were detected in the APAP group. Combined NAC+CsA treatment sufficiently reversed oxidative stress, serum Cr and BUN levels and histopathological alterations induced by APAP. Moreover, cytc levels and renal tubular injury were remarkably reduced by combined drug treatment compared to the APAP+NAC group. These data suggest that the therapeutic effect of combined NAC+CsA treatment in mice with APAP-induced nephrotoxicity can be related to the combination of the antioxidant effect of NAC and the mitochondrial MPTP inhibitor effect of CsA.

Influence of Pre-treatment of Withania somnifera Root Extract and Cow Urine on Hemato-biochemical Parameters in Acetaminophen-induced Toxicity in Swiss Albino Male Mice

Effects of Concomitant Use of N-acetylcysteine and Cyclosporine A on Acetaminophen-induced Acute Kidney Injury in Mice