Therapeutic Efficacy of Ursodeoxycholic Acid (Fortibile® tablet) on Nonsteroidal Anti-Inflammatory Drug (NSAID)-induced Hepatic Dysfunction in Experimental Animals

Background: Hepatotoxicity is one of the common side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Scientific study stated that hepatotoxicity is the most serious adverse effects of Aceclofenac. Objectives: In this study, our aim was to investigate the use of Fortibile® tablet containing ursodeoxycholic acid (UDCA) in prevention of the hepatotoxic effect and biochemical changes induced by aceclofenac (ACE) in laboratory mice. Materials and Methods: Swiss albino mice were divided into four groups (control, UDCA (Fortibile® tablet) 20 mg/kg, aceclofenac (ACE) 50mg/kg, UDCA 20 mg/kg + aceclofenac 50 mg/kg). Results: Administration of aceclofenac (ACE) showed decline body weight, food consumption, water intake and elevated liver weight in mice whereas treatment with UDCA (Fortibile® tablet) normalized the same as compared with untreated animals. Animals treated with aceclofenac caused elevated activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) as well as total and direct bilirubin level. These elevations in liver enzymes were decreased by combination of aceclofenac with UDCA. On the other hand application of aceclofenac (ACE) on mice caused a significant increase in serum and tissue malondialdehyde (MDA) and nitric oxide (NO) content but significant decrease in glutathione GSH and GPx content. Combine thepary of UDCA and aceclofenac resulted in a significant decrease in MDA, NO content and significantly elevated GSH and GPx content. Conclusion: It could be concluded that Fortibile® tablet containing Ursodeoxycholic acid acts as an effective hepatoprotective agent against NSAIDs induced liver dysfunction, and this effect might be related to its antioxidant properties. Hepatic functions should be monitored, and the dose should be adjusted during aceclofenac (ACE) therapy. Keywords: Ursodeoxycholic acid, Aceclofenac, Hepatotoxicity, Liver function test, Oxidative stress,

Investigating Jaundice in the Newborn

JAUNDICE IS OFTEN SEEN IN the neonatal period, with 60 percent of full-term and 80 percent of preterm infants having visible jaundice.1 Jaundice is a sign of hyperbilirubinemia, which, in the newborn period, is usually due to an elevated indirect or unconjugated bilirubin level, and may result from an exaggerated physiologic response or be pathologic in nature. Hyperibilirubinemia due to an elevated direct or conjugated bilirubin is less common. Although an elevated direct bilirubin level can be transient, it is often related to some pathology.

Evaluation and Treatment of Jaundice in the Term Newborn: A Kinder, Gentler Approach

Standard recommendations for evaluating and treating jaundice in term babies include following all babies closely for jaundice, obtaining several laboratory tests in those with early jaundice or bilirubin levels more than 12 to 13 mg/dL (205 to 222 µmol/L), using phototherapy to try to keep bilirubin levels below 20 mg/dL (342 µmol/L), and doing exchange transfusions if phototherapy fails, regardless of the cause of the jaundice. These recommendations are likely to lead to unnecessary testing and treatment of many jaundiced term infants. Because most jaundiced infants have no underlying illness, and the generally recommended laboratory tests lack sensitivity and specificity, they are seldom useful. In most babies, the only blood tests needed to evaluate jaundice are the blood type and group (of baby and mother) and a direct Coombs' test. A determination of direct bilirubin level should be added if jaundice is prolonged (>2 to 4 weeks) or the baby has other signs of illness. Bilirubin toxicity is rare in term babies without hemolysis. In this low-risk group, the risks and cost of identifying and treating high bilirubin levels may exceed the benefits. Such infants need not be closely followed for jaundice. If significant jaundice is nonetheless found, treatment should be deferred to relatively high levels of serum bilirubin, with a goal of keeping bilirubin levels below 400 to 500 µmol/L (23.4 to 29.2 mg/dL). Babies with hemolytic disease should be followed more closely, and their bilirubin levels kept below 300 to 400 µmol/L (17.5 to 23.4 mg/dL). These recommendations should be reevaluated as new data become available. In the meantime, currently available data justify an approach to the jaundiced term infant that is less aggressive than previously recommended.

THE TEN COMMANDMENTS OF PHOTOTHERAPY

Thou shalt 1. Not use phototherapy prior to determination of etiology.1,2 2. Not use phototherapy in infants with direct hyperbilirubinemia (conjugated direct bilirubin level > 2 mg/100 ml).1,3 3. Not judge jaundice clinically in infants treated with phototherapy, but measure serum bilirubin level every 4 to 12 hours as indicated.1,2 4. Monitor temperature of infants placed under phototherapy initially every hour for the first four hours and thereafter every four to six hours.2,3 5. Weigh low-birth-weight infants receiving phototherapy twice daily. Increase their fluid intake above requirements by 2% to 10% depending on postnatal age, cardiac status, and whether the infant is under a radiant warmer or an adequately humidified incubator.1,3 6. Protect eyes with adequately designed patches. Turn off light and remove eye patches when parents are visiting.2,3 7. Monitor hematocrit value, particularly in hemolytic diseases.1,2 8. Watch for rebound of bilirubin level following discontinuation of phototherapy. Delay discharge by about 6 to 12 hours till rebound can definitely be ruled out.2 9. Change the lamps after 20% decrease of original irradiance output. Consult with the manufacturer of the individual lamps used, or energy output in the blue spectrum (425 to 475 mm) every 200 hours of use.1,2 10. Check all phototherapy units for proper electrical grounding.