THE ROLE OF GARLIC IN THE PREVENTION OF DRUG AND CHEMICAL INDUCED TOXICITY

1. THE ROLE OF GARLIC IN THE PREVENTION OF DRUG AND CHEMICAL INDUCED TOXICITY EVIDENCE FROM PUBLISHED LITERATURE

2. Prof Christian C EzealaPhD, MSc, AMLSCN, MICR, MSB, CBiol, CSci, FSAFRI, FASICollege of Medicine, Nursing, & Health Sciences

3. Background • Drug and chemical induced toxicity is a common cause of hospital admissions in both developed and developing countries • Garlic is widely used as spice and in many traditional medical practices • Garlic has many pharmacologically active constituents • Studies have shown these to exert effective protection against drug and chemical induced toxicity

4. AIM • To present current evidence from published literature on the usefulness of garlic and its products in preventing chemical induced toxicity

5. Objectives • To determine from peer reviewed literature, the toxicity models in which garlic has been reported to exert protective effect; • To articulate suggested mechanisms for this toxicoprotection; • To determine the constituents that were reported to be toxicoprotective • Appraise the studies for their strength of evidence.

6. Methods • Systematic review of literature designed to answer the questions: • “Does garlic prevent drug and chemical induced toxicity?” • By what mechanisms is this protection? • Which constituents protect against toxicity?

7. Article Selection Criteria • Articles that report results of a primary research • Study design is experimental, preclinical or clinical studies inclusive • Studies that involve accidental or intentional chemical or drug induced toxicity in mammalian species, isolated organs, or mammalian cell lines; • Organs or systems toxicity were investigated • Positive and negative controls and/or a standard drug (or standard of care) were included; • Study endpoints included biochemical, hematological, physiological, and/or histological assessments • Time limits – articles published in the last 20 years (1994-2013)

8. Literature Search Strategy • Search terms used included “garlic” OR “Allium sativa;” “chemical induced” OR “drug induced;” “toxic*”; “protect*” OR “prevent*” • Search engines and databases used included PubMed/Medline, Google Scholar, Microsoft academic search, and High Wire Press. • Time limits set to articles published between Jan 1994 and December 2013.

9. Data Collection and Analysis • Articles that met the above criteria were analyzed and the following information extracted: • Type of garlic preparation or constituent used • Toxicity model studied • Endpoints measured • Reported mechanisms

10. Toxicity Models

11. Toxicity Models

12. Garlic Preparations or Constituents Used • Fresh garlic • Aged garlic extract • Aqueous extract • Alcoholic or organic extract • Garlic oil • Purified constituents: • Diallyl sulfide (DAS) • Diallyl disulfide (DADS) • Diallyltrisulfide (DATS) • Thiacremonone • S-allylmercaptocysteine (SAMC) • S-allylcysteine (SAC)

13. Chemical Constituents Allicin (diallylthiosulphinate) Diallyldisulphide (DADS) Alliin (S-allylcysteinesulphoxide)

14. Mechanisms of Toxicoprotection

15. Conclusion • Garlic derived products exert toxicoprotective effects by several mechanisms including antioxidant and anti-inflammatory effects, inhibition of bioactivation by CYP enzymes, and inhibition of apoptosis. • Garlic products used in studies included crude and purified constituents • A wide variety of toxicity models were described including hepatotoxicity, carcinogenesis, and neurobehavioural toxicity. • All the studies were preclinical, posing restrictions on extrapolation of the results to the clinical setting