HEPATOCYTE APOPTOSIS INDUCTION BY ACETAMINOPHEN THROUGH MODULATION OF CASPASE/BAX PATHWAY IN MICE

Objective: Acetaminophen (APAP) overdose contributes to liver damage through modulation of pro-apoptotic processing. This study evaluated the involvement of caspase/Bax factors in APAP hepatotoxicity in vivo and in vitro. Methods: The involvement of caspase/Bax factors in APAP hepatotoxicity was evaluated in BALB/c mice and on isolated primary mouse hepatocytes. In vitro MTT assay was carried out on primary cultured mouse hepatocytes treated with APAP (2.5, 5, 10 mmol) and Annexin V/PI staining was employed to cell suspension for imaging under fluorescence microscopy. In addition, caspase-3 concentrations were determined in cell lysates. In vivo, mice were treated with a toxic dose of APAP (700 mg/kg) and immunodetection of Bax was made by Western Blot. Vitamin C (Vit C) was used as a hepato-protectant due to its known antioxidant activities. Results: In vitro dose-dependent increase in mitochondrial electron transport capacity was evident in isolated mouse primary hepatocytes incubated with the high dose of APAP (10 mmol) compared to both nontreated cells and cells pre-treated with Vitamin C (Vit C) (0.5 mmol) (p<0.05). Apoptosis was confirmed in hepatocytes through Annexin V staining after APAP treatment and the signal was reduced when hepatocytes were pre-treated with Vit C. In addition, caspase-3 concentration was decreased in cells pretreated with Vit C prior to APAP exposure. In vivo, Bax immunodetection utilizing western blotting was increased in mice treated with the toxic dose of APAP (700 mg/kg) and attenuated through pre-treatment with Vit C. Conclusion: Modulation of apoptotic caspase/Bax pathway is present in hepatocytes undergoing APAP-induced toxicity

Lysionotin exerts antinociceptive effects in various models of nociception induction

Background: Lysionotin, a natural flavonoid extracted from Lysionotus pauciflorus Maxim (Gesneriaceae), has several pharmacological effects including anti-bacterial, anti-hypertensive and anti-inflammatory effects. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of lysionotin using chemically and thermally induced nociception in a mouse model. Methods: The antinociceptive effects of various lysionotin doses (50, 100, 150, and 200 μg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone (an opioid receptor antagonist). Capsaicin- and glutamate-induced paw licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Results: Lysionotin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 60% inhibition at a dose of 200 μg/kg. Lysionotin also caused a significant increase in the latency period in response to the hot plate test (76.4% at 200 μg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw licking test. Naloxone significantly reverses the effect of lysionotin in both hot plate test and formalin-induced paw licking test. Moreover, lysionotin significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (57% and 67.2%, respectively at a dose of 200 μg/kg). Thus, lysionotin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system. Conclusion: Lysionotin possesses antinociceptive activity on adult mice that is mediated through both central and peripheral pathways

An audit on parental attitudes towards medicines used in children

Introduction There is growing concerns regarding the use of medicines in children. Therefore, many strategies were implemented to improve such use and make safe and effective medicines more available for children. Enhancing interaction between parents and health care providers plays an important role in insuring the proper use of medicines. In order to optimize such interaction, the attitudes, beliefs and practices of parents toward medicine use in children need to be explored. Methods A validated questionnaire was administered via face to face interviews to 1000 parents attending pediatric outpatient clinics with their children in order to investigate their attitudes toward children's medicines. Results The majority of respondents (83.2%) were mothers. The majority participants (84.4%) agreed that medicines are necessary in treating illnesses, 80% of the parents had worries about the side effects and interactions of medicines, and 60% of the parents said they try to avoid giving medicines to their children. Moreover, parents in this study varied considerably in their views toward prescription and over-the- counter medicines. More than half of the participants (55.2%) declared that doctors in Jordan prescribe antibiotics to children too easily. Conclusion Participants had positive attitudes toward the necessity of medicines for ill children. However, a considerable proportion of the parents had negative attitudes toward children's medicines with respect to their side effects and interactions, their capability of disturbing the body's own capability of healing illnesses, their unnatural characteristic and other aspects related to medicines

An audit on parental attitudes towards medicines used in children

Introduction: There is growing concerns regarding the use of medicines in children. Therefore, many strategies were implemented to improve such use and make safe and effective medicines more available for children. Enhancing interaction between parents and health care providers plays an important role in insuring the proper use of medicines. In order to optimize such interaction, the attitudes, beliefs and practices of parents toward medicine use in children need to be explored. Methods: A validated questionnaire was administered via face to face interviews to 1000 parents attending pediatric outpatient clinics with their children in order to investigate their attitudes toward children's medicines. Results: The majority of respondents (83.2%) were mothers. The majority participants (84.4%) agreed that medicines are necessary in treating illnesses, 80% of the parents had worries about the side effects and interactions of medicines, and 60% of the parents said they try to avoid giving medicines to their children. Moreover, parents in this study varied considerably in their views toward prescription and over-the- counter medicines. More than half of the participants (55.2%) declared that doctors in Jordan prescribe antibiotics to children too easily. Conclusion: Participants had positive attitudes toward the necessity of medicines for ill children. However, a considerable proportion of the parents had negative attitudes toward children's medicines with respect to their side effects and interactions, their capability of disturbing the body's own capability of healing illnesses, their unnatural characteristic and other aspects related to medicines. Keywords: Parents, Attitudes, Medicines, Children, Jorda