HISTOPATHOLOGY AND THERAPEUTIC EFFECTS OF METHANOLIC SEED EXTRACT OF ARTOCAPUS ALTILIS ON PARACETAMOL INDUCED LIVER DAMAGE IN WISTAR RATS

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HISTOPATHOLOGY AND THERAPEUTIC EFFECTS OF METHANOLIC SEED EXTRACT OF ARTOCAPUS ALTILIS ON PARACETAMOL INDUCED LIVER DAMAGE IN WISTAR RATS

CHAPTER ONE:

INTRODUCTION

Background

Liver damage induced by drugs, toxins, and chemicals is a significant health concern globally. Among the substances implicated in liver injury is paracetamol (acetaminophen), a widely used analgesic and antipyretic agent. Despite its efficacy, overdose or prolonged use of paracetamol can lead to hepatotoxicity, characterized by liver cell necrosis and dysfunction. This hepatotoxic effect has prompted research into potential therapeutic agents that could mitigate or reverse paracetamol-induced liver damage.

Arthocarpus altilis and Its Therapeutic Potential

Arthocarpus altilis, commonly known as breadfruit, belongs to the Moraceae family and is cultivated in tropical regions worldwide. In traditional medicine, various parts of Arthocarpus altilis have been used to treat ailments ranging from hypertension to skin diseases. The seeds of Arthocarpus altilis contain bioactive compounds such as phenolics, flavonoids, and alkaloids, which possess antioxidant and hepatoprotective properties.

Liver damage remains one of the most serious complications of drug toxicity, with paracetamol (acetaminophen) overdose being one of the leading causes of acute liver failure worldwide. Paracetamol is commonly used for its analgesic and antipyretic properties, but its misuse or overdose can lead to severe hepatotoxicity. The liver metabolizes paracetamol primarily through glucuronidation and sulfation pathways; however, a small portion is converted by the cytochrome P450 enzyme system into N-acetyl-p-benzoquinone imine (NAPQI), a highly reactive and toxic metabolite. Under normal conditions, NAPQI is detoxified by conjugation with glutathione, but in overdose scenarios, glutathione stores become depleted, leading to the accumulation of NAPQI and subsequent oxidative stress, inflammation, and liver cell necrosis.

The current standard treatment for paracetamol-induced liver damage is N-acetylcysteine (NAC), which replenishes glutathione levels and detoxifies NAPQI. However, NAC therapy has limitations, including the necessity for early administration within a narrow therapeutic window and the risk of adverse reactions in some patients. These challenges have driven the search for alternative or adjunctive therapies that can provide effective hepatoprotection with a broader therapeutic window and fewer side effects.

Artocarpus altilis (breadfruit) is a tropical plant known for its nutritional and medicinal properties. The seeds of Artocarpus altilis are particularly rich in bioactive compounds, including flavonoids, phenolic acids, and antioxidants, which have been shown to possess various pharmacological activities, such as anti-inflammatory, antimicrobial, and antioxidant effects. Traditional uses of Artocarpus altilis in treating various ailments have prompted scientific investigations into its potential therapeutic benefits.

Recent studies have suggested that the methanolic seed extract of Artocarpus altilis may exhibit hepatoprotective effects, making it a promising candidate for mitigating drug-induced liver damage. However, there is a lack of comprehensive studies that specifically evaluate the histopathological and therapeutic effects of Artocarpus altilis seed extract on paracetamol-induced liver injury.

This study aims to investigate the protective effects of methanolic seed extract of Artocarpus altilis on paracetamol-induced liver damage in Wistar rats. By examining histopathological changes and biochemical markers of liver function, this research seeks to provide insights into the potential use of Artocarpus altilis as a natural therapeutic agent for liver protection, thereby contributing to the development of novel treatments for drug-induced hepatotoxicity.

Statement of the problem

Liver damage caused by paracetamol (acetaminophen) overdose is a significant public health concern due to its widespread use as an over-the-counter analgesic and antipyretic. Paracetamol-induced hepatotoxicity is primarily attributed to the excessive production of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which leads to oxidative stress, inflammation, and necrosis of liver cells. The increasing incidence of paracetamol-induced liver injury underscores the need for effective therapeutic interventions to mitigate its harmful effects.

Current treatments, such as N-acetylcysteine (NAC), are effective but have limitations, including the need for early administration and potential side effects. As a result, there is a growing interest in exploring alternative natural therapies with fewer side effects and broader therapeutic windows.

Artocarpus altilis (breadfruit) has been traditionally used for various medicinal purposes, and recent studies have suggested that its methanolic seed extract may possess hepatoprotective properties due to its rich content of antioxidants, anti-inflammatory compounds, and bioactive phytochemicals. However, the specific therapeutic effects of Artocarpus altilis seed extract on paracetamol-induced liver damage have not been thoroughly investigated.

This study aims to address this gap by evaluating the histopathological and therapeutic effects of the methanolic seed extract of Artocarpus altilis on paracetamol-induced liver damage in Wistar rats. The findings of this research could provide valuable insights into the potential use of Artocarpus altilis as a natural therapeutic agent for liver protection and contribute to the development of alternative treatments for drug-induced hepatotoxicity.

Rationale for the Study

Despite its traditional use and potential therapeutic benefits, the specific effects of methanolic seed extract of Arthocarpus altilis on paracetamol-induced liver damage have not been extensively studied. Understanding these effects could pave the way for developing new therapeutic approaches for managing drug-induced liver injury, particularly from paracetamol overdose.

Objectives of the Study

To investigate the histopathological changes in the liver induced by paracetamol in Wistar rats.

To evaluate the therapeutic effects of methanolic seed extract of Arthocarpus altilis on paracetamol-induced liver damage.

To assess biochemical markers of liver function in Wistar rats treated with Arthocarpus altilis seed extract following paracetamol-induced liver injury.

Significance of the Study

This study aims to contribute to the understanding of the therapeutic potential of Arthocarpus altilis in mitigating paracetamol-induced liver damage. The findings could provide valuable insights into the development of novel hepatoprotective agents and enhance treatment strategies for drug-induced liver injury.

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