ABSTRACT

The aim of the study was to investigate effects of kaempferol and zinc gluconate administration on haematological, neurobehavioural and oxidative stress changes in Wistar rats, exposed to noise stress. Thirty (30) rats were randomly divided into five groups: Groups I and II were administered with deionised water; Group III, kaempferol; Group IV, zinc gluconate; Group V, kaempferol + zinc gluconate for 36 days. Groups II, III, IV and V were subjected to noise stress of 100 dB dose for 15 days from day 22 to day 36. Behavioural activities were assessed on days 1, 8 and 15 after noise exposure. The effects of the different treatments on body weight change, open-field activities, neuromuscular coordination, motor strength, excitability scores, sensorimotor reflexes and learning and memory were assessed in the rats. Packed cell volume, haemoglobin concentration,    total                            erythrocyte                 count,     erythrocytic     indices,     platelet     count neutrophil/lymphocyte ratio, total and differential leucocyte counts and erythrocyte osmotic fragility (EOF) test were determined using standard methods. The brain was used to evaluate noise stress-induced lipoperoxidative changes, through determination of brain malondialdehyde (MDA) concentration and activities of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase, using kits. The results of this study showed that noise stress-induced decrease in body weight gain was significantly (P < 0.05) ameliorated in the group treated with kaempferol + zinc (123.70 ± 0.99 g, 133.70 ± 1.59 g) than in the group treated with deionised water + noise (117.70 ± 1.02 g, 125.70 ± 1.20 g). There was a significant and consistent decrease in the EOF of rats treated with kaempferol + zinc. Kaempferol + zinc gluconate significantly (P < 0.05) ameliorated decrease in haemoglobin concentration (from 12.62 ± 0.12 to 14.32 ± 0.11 g/dL), packed cell volume (from 37.85 ± 0.35 to 43.47 ± 0.30 %) and erythrocyte counts (from 6.43 ± 0.04 to 7.20 ± 0.06× 1012/L). Values of mean corpuscular haemoglobin (20.40 ± 0.33 ρg) and mean corpuscular haemoglobin concentration (33.20 ± 0.15%) were significantly (P < 0.05) higher in kaempferol + zinc treated rat compared to the deionized water + noise treated group (18.43 ± 0.34) and (29.65 ± 0.89) respectively. Rats treated with zinc had the highest mean corpuscular volume (61.35 ± 0.67 fL) compared to the deionized water + noise treated group (58.87 ± 0.29). Platelet counts were also significantly higher (P < 0.05) in rats treated with kaempferol + zinc (609.20 ± 6.90 x 106 g/dL) compared to the group treated with noise + deionised water (439.80 ± 7.91 x 106 g/dL). Administration of kaempferol + zinc caused leucocytosis due to neutrophilia and lymphocytosis as well as a significant (P < 0.05) decrease in N:L ratio (0.25 ± 0.01) than in the group treated with deionised water + noise (0.35 ± 0.03). Combination kaempferol + zinc significantly (P < 0.05) enhanced learning (from 2.33 ± 0.33 s to 1.17 ± 0.17) and memory (from 92.17 ± 4.08 s to 106.80 ± 2.14 s). Kaempferol + zinc significantly (P < 0.05) mitigated noise stress induced impairment in neuromuscular coordination neuromuscular coordination (from 45.0 ± 1.43o to 65.06 ± 1.23o), motor strength (from 51.68 ±229 s 78.33 ± 5.69 s), sensory motor reflex (from 2.88 ± 0.16 to 4.83 ± 0.17), and motor coordination on days 1, 8 and 15 (from 10.83 ± 1.40 cm, 11.5 ± 1.18 cm, 10.50 ± 0.923 cm to 5.33 ± 1.45 cm, 4.33 ± 1.41 cm and 4.83 ± 1.35 cm) respectively. Kaempferol + zinc exerted anxiolytic effects, demonstrated in treated rats subjected to open-field test. In addition, combined treatment significantly (P < 0.05) decreased malondialdehyde (MDA) concentration (from 1.10 ± 0.20 nmol/mg to 0.70 ± 0.20 nmol/mg) and enhanced activities of

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CHAPTER ONE:

1.0 INTRODUCTION

1.1 Background of the Study

Noise is derived from the Latin term „nausea‟ and has been defined as unwanted sound,

which is a potential hazard to communication and health (Ismaila and Odusote, 2014).

Stress refers to a non-specific response of the body to unpleasant stimuli, threatening

homeostasis and the integrity of the organism (Wankhar et al., 2014; Munne-Bosch and

Pinto-Marijuan, 2017). It is a state of threatened homeostasis provoked by psychological,

physiological and environmental stressors (Zhang et al., 2015). Noise is measured in

decibel (dB) units (Ismaila and Odusote, 2014). Wang et al. (2016) reported that noise

exposure is a potent stressor as it increases the levels of the stress hormone,

corticosterone. Noise pollution, especially in the urban environment, is on the increase

(Öhrström et al., 2006; Michaud et al., 2016; WHO, 2016) and ranks among the

environmental stressors with the highest public health impact (WHO, 2016). The auditory

effects include hearing impairment and permanent hearing loss due to excessive noise

exposure. The non-auditory effects include stress-related, physiological and behavioural

effects.

Noise stress induces increased reactive oxygen and nitrogen species (ROS and RNS)

generation, which are capable of breaking down lipid and protein molecules and

damaging DNA, triggering loss of function and cell death (Henderson et al., 2006; Zhang

et al., 2015). The ROS also trigger apoptosis by activating proapoptotic mitogen

activated protein (MAP) kinase-signaling pathways (Tao et al., 2015). Oxidative

1

destruction has been associated with ROS-induced diseases (Messarah et al., 2011).

Antioxidants are molecules that inhibit and scavenge ROS/RNS and convert them to less

dangerous molecules (Michael and Peter, 2015).

1.2 Statement of Research Problem

Noise-induced hearing loss has global implications, with 10 million adults and 5.2

million children in the US, and 250 million people world-wide having a noise-induced

hearing loss greater than 25 dB; a clinically significant hearing loss (Tao et al., 2015).

Additionally, occupational noise accounts for 16% of the disabling hearing loss in adults

world-wide, resulting in decreased economic production (Baliatsa et al., 2016). Nocturnal

environmental noise also provokes measurable metabolic and endocrine perturbations,

including secretion of adrenaline, noradrenaline, cortisol, increase