Skip to main content

Induction of Mitochondrial-Mediated Apoptosis by Solvent Fractions of Methanol Extract of Heliotropium indicum in Rat Liver Cells | Chapter 10 | Recent Advances in Biological Research Vol. 4

Introduction: The biochemical process of apoptosis may occur by a number of mechanism including; extrinsic or death-receptor pathway, intrinsic or mitochondrial-mediated pathway which involves the opening of Mitochondrial Membrane Permeability Transition (MMPT) pore in situations of intracellular calcium overload or oxidative stress or cellular insult and by the perforin/granzyme pathway. There is considerable evidence that bioactive agents in some plants (sulforaphane in cruciferous vegetables, genistein in soybeans and epigallocatechin gallate in green tea etc.) were able to induce MMPT pore opening. Quite a number of these agents have been identified and they currently under preclinical and clinical trials.



Aim: Mitochondrial Membrane Permeability Transition (MMPT) pore has emerged as a promising target for drug development because the release of cytochrome c upon the opening of the pore is a point of no return for mitochondrial-mediated apoptosis to occur. Heliotropium indicum (HI) is as an anti-tumor and wound healing agent in traditional medicine. It is not known whether its mode of action involves the induction of apoptosis via the opening of the MMPT pore.

Methodology: Mitochondria, isolated from male albino rat liver (about 100 g), were exposed to varying concentrations (10, 30, 50, 70, and 90 µg/ml) of  solvent fractions of  methanol extract of HI  i.e  Chloroform (CFHI), Ethylacetate (EFHI), Methanol (MFHI)  and crude  Methanol Extract (MEHI) of HI. Opening of the pore, cytochrome c release, mitochondrial ATPase activity and extent of mitochondrial lipid peroxidation were assessed spectrophotometrically in vitro. Activation of caspases 9 and 3 were also assessed using ELISA kits.

Results: In the absence of Ca2+, CFHI, EFHI, MFHI and MEHI induced the opening of the pore in a concentration-dependent manner with CFHI having the highest induction fold of 26 and MFHI as the lowest having 6.6. All the fractions inhibited lipid peroxidation in a concentration-dependent manner. Also, these fractions induced the release of cytochrome c with CFHI having the highest effect and the least by MFHI. Mitochondrial ATPase activity was enhanced by all the fractions with CFHI having the highest stimulatory effect. Interestingly, intra-peritoneal administration of CFHI and MEHI at 2, 5, 10 and 20 mg/kg body weight for 21 days resulted in significant opening of the pore, the release of cytochrome c and activation of caspases 9 and 3. All these effects were highest with 20 mg/kg body weight.

Conclusion: These findings therefore suggest that Chloroform Fraction of Heliotropium indicum is the most potent of all these fractions and therefore contains the bioactive agent that induces mitochondrial-mediated apoptosis in normal liver cells. The fraction will therefore be useful for further studies for drug development in diseases requesting up-regulation of apoptosis.

Author(s) Details

Adeola O. Olowofolahan
Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.

Yemisi D. Adeoye
Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.

Olufunso O. Olorunsogo
Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.

View Volume: https://doi.org/10.9734/bpi/rabr/v4

Comments

Popular posts from this blog

A Brief Study of Middleware Technologies: Programming Applications and Management Systems | Chapter 15 | Novel Research Aspects in Mathematical and Computer Science Vol. 1

  Many platforms, services, applications, hardware, and operating systems are connected through the middleware layer. Because the middleware layer abstracts much low-level complexity and makes applications and software systems portable, it allows disparate systems to interface and function together in harmony. Middleware technologies enable software engineers to swiftly construct software systems and applications, allowing developers to focus on more important tasks. This chapter examines several types of middleware systems and discusses middleware capabilities, middleware operation, middleware's function in cloud-based systems, and the best middleware platforms to use. Middleware systems are widely utilised and can be found in practically any software system or application. Middleware programmes provide as a link between many sorts of systems and protocols. They serve as a mechanism for various systems. To successfully exchange information, it runs on a variety of operating system

A Prospective Study about Safety and Efficacy of Perioperative Lidocaine Infusion | Chapter 09 | New Horizons in Medicine and Medical Research Vol. 8

 Opioids cause clinically significant side effects such as respiratory depression, immunosuppression, muscle rigidity, negative inotropism, nausea, vomiting, hyperalgesia, urine retention, postoperative ileus, and drowsiness. Perioperative opioids are a major contributor to the United States' and other countries' opioid epidemics. Non-opioid analgesics, particularly lidocaine, are becoming more common for perioperative use as a result of this. A total of 185 adult patients were randomly assigned to one of two groups: control group I (105 patients) [fentanyl group] or group ii (80 patients) [opioid-free anaesthesia group]. Lidocaine 1.5 mg/kg bolus followed by 1.5 mg/kg/h infusion intraoperatively, and 1.5-2 mg/kg/h infusion for 2-8 hours postoperatively were given to patients in both groups at anaesthetic induction. Intraoperatively, both groups received analgesic adjuvants such as diclofenac 75 mg, paracetamol 1 gm, and mgso4 30-50 mg/kg. If the mean arterial pressure (map)

Patients’ Perspective of Acute Post-operative Pain Management: A Multicentre Survey of Tertiary Hospitals in Maharashtra, India | Chapter 08 | New Horizons in Medicine and Medical Research Vol. 8

 When postoperative pain is adequately controlled, patients' satisfaction and patient-related outcomes (PROs) increase. Understanding the patients' perspective is crucial since it supports in the formulation of improvement strategies. Because wrong attitudes and assumptions might block pain alleviation, patients' attitudes and beliefs are critical. As a result, a multicenter study of patients' attitudes, beliefs, experiences, and satisfaction levels with acute postoperative pain management was done in Maharashtra's tertiary hospitals. In addition, the responses were examined to evaluate if the Acute Pain Service (APS) resulted in improved patient outcomes and satisfaction. A 13-item questionnaire adapted from previous studies was used to capture patients' experiences with postoperative pain treatment. The responses of 179 patients are included in the study. The findings revealed that 91.6 percent of patients experienced postoperative pain, with 75.5 percent