Neurobehavioural and neurohistological effects of Nigella sativa after neurotoxicant toluene administration in mice / Nur Lisa Mohd Yusoff

Nur Lisa , Mohd Yusoff (2022) Neurobehavioural and neurohistological effects of Nigella sativa after neurotoxicant toluene administration in mice / Nur Lisa Mohd Yusoff. Masters thesis, Universiti Malaya.

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Abstract

Humans are readily exposed to the environmental pollutant toluene, commonly in small amount, e.g., from daily household products, petroleum, and occupational settings. Reports showed that toluene toxicity is detrimental to human physiological systems, especially the central nervous system (CNS). Hence, the intensive search for substances that can offer neuroprotection, ideally, sourced from the natural product, considering it to be less costly and possibly with less side effects. One such candidate is the Nigella sativa (NS), a traditionally consumed natural supplement, also known to have antioxidant properties and the potentials for neuroprotective effects. The current study aimed to investigate NS protective potentials from neurobehavioural aspect through recognition memory and neurohistological aspect of hippocampal region of mice exposed to toluene. The study consisted of three main experiments: Experiment 1 (preliminary toluene toxicity test), Experiment 2 (preliminary Novel Object Recognition (NOR) behavioural test), and Experiment 3 (NS neuroprotective test). Experiment 1 and 2 were conducted to determine the toluene dosage capable of causing the highest abnormalities in the brain of the experimental animals as well as its consequent effects on learning and behaviour. From the two preliminary tests, 500 mg/kg toluene caused the most recognition memory impairment in NOR and demonstrated smaller hippocampal neuron size in mice brain. Adult male ICR mice (8 weeks old) were used in this study. For all three tests, corn oil was used as the control. In the NS neuroprotective test, treatments were conducted for 14 consecutive days. Mice were orally supplemented from day 1 and continued until day 14 with three different forms of NS: NS seeds (NSS), NS oil (NSO), and its selected bioactive NS constituent, thymoquinone (TQ). Toluene was intraperitoneally injected (i.p.) in mice starting from day 7 until day 14. Following the treatments, NOR test was conducted, and mice were intracardially perfused. Brain was collected, histologically processed and Nissl stained with Cresyl Violet dye. Brain gross morphology was measured, and then somatic size and shape of hippocampal CA1 pyramidal neurons were quantified according to specific morphometric parameters. Results from the current study showed that toluene had the tendency to reduce recognition memory performance of mice and somatic size of hippocampal CA1 pyramidal neurons. Contradictorily, the other treatments, especially involving TQ, NSO, and NSS improved the mice recognition memory and somatic size of hippocampal CA1 pyramidal neurons. Meanwhile, brain morphology and somatic shape of hippocampal CA1 pyramidal neurons showed no significant differences between all NS treatment groups. The key findings from the current study concluded that 500 mg/kg toluene could cause impairment, while NS induced improvement of mice neurobehavioural performance and neurohistological brain and neuronal structure, though not significantly.

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