Post-liver resection mortality does not correlate to remnant liver volume in selected patients with remnant liver volume to body weight ratio exceeding 0.5%

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

Download Full-text

Exercise and clenbuterol as strategies to decrease the progression of muscular dystrophy in mdx mice

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.3.734 ◽

1996 ◽

Vol 80 (3) ◽

pp. 734-741 ◽

Cited By ~ 24

Author(s):

E. E. Dupont-Versteegden

Keyword(s):

Body Weight ◽

Muscular Dystrophy ◽

Weight Ratio ◽

Morphological Characteristics ◽

Mdx Mice ◽

Body Weight Ratio ◽

Muscle Weight ◽

Sedentary Group ◽

Running Activity ◽

Tetanic Tension

The effects of exercise and the combination of exercise and clenbuterol on progression of muscular dystrophy were studied in mdx mice. At 3 wk of age, mdx mice were randomly assigned to sedentary (MS), exercise (ME), or combined exercise and clenbuterol (MEC) groups. Clenbuterol was given in the drinking water (1.0-1.5 mg . kg body weight-1 . day-1), and exercise consisted of spontaneous running activity on exercise wheels. At 3 mo or 1 yr of age, ventilatory function, contractile properties, and morphological characteristics of the soleus (Sol) and diaphragm (Dia) muscles were measured. The mdx mice receiving clenbuterol ran less than the mice without clenbuterol. The combination of clenbuterol and exercise was associated with an increase in Sol muscle weight and a muscle weight-to-body weight ratio of 30-35% compared with the sedentary group and approximately 20% compared to exercise alone. Myosin and total protein concentrations of the Sol and Dia increased in the MEC group at 1 yr of age only. Normalized active tension was increased in the Dia at 1 yr of age in both the ME and MEC groups by approximately 30%. Absolute tetanic tension of the Sol was increased at both 3 mo and 1 yr of age in the MEC compared with the MS group. At 1 yr of age, there was an additional 23% increase compared with the ME group. Fatigability increased in the MEC group by approximately 25% in the Sol and Dia muscles at both ages compared with the MS and ME groups. Results indicate that exercise and exercise plus clenbuterol decrease the progression of muscular dystrophy. However, different mechanisms may be involved because the combination of clenbuterol and exercise resulted in increased fatigability and the development of deformities, whereas exercise alone did not. Therefore, clenbuterol may not be suitable for use in patients with muscular dystrophy.

Download Full-text

A study on the safety evaluation of buphrenorphine administered through an autoinjector compared with manual injection using haematological and biochemical variables in rats

Human & Experimental Toxicology ◽

10.1177/0960327116674528 ◽

2016 ◽

Vol 36 (9) ◽

pp. 901-909 ◽

Cited By ~ 1

Author(s):

D Sheela ◽

R Vijayaraghavan ◽

S Senthilkumar

Keyword(s):

Body Weight ◽

Research Work ◽

Safety Evaluation ◽

Weight Ratio ◽

The Body ◽

Control Group ◽

Body Weight Ratio ◽

Significant Difference ◽

Manual Group ◽

Significant Change

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.

Download Full-text