Diverse variety of Nigerian plants and their by-products finds wide use in Nigerian ethnobotany as food, dietary, and herbal medicinal components. Their bioactive phytochemicals and biomolecules constituents, e.g. polyphenols, carbohydrates, proteins, minerals and oils confers such utilitarian values.[1] In turn, thousands of these plant products are used daily for herbal medicinal and dietary purposes. Health management in Nigeria is presently suboptimal as a result medicinal plants find wide application in herbal remedies alongside orthodox medical practice. Unfettered herbal medical practice is prevalent and considered safe by tradition passed down over several 100 of years, without orthodox scientifical toxicological assessment and standardized procedures. Nigerian indigenous flora till date continues to contribute vastly in the delivery of health care to its populace,[234] irrespective of the limited knowledge on the pharmacological efficacies of most of these herbs,[5] their spectrum of activity and conceivably associated toxicities. Amongst others, Keayodendron bridelioides (KB) and Monodora myristica (MM) are commonly found in Nigerian Ethnobotany and used as herbal medicinal constituents[6] and food additives to spice up local cuisine. Both KB and MM when used as a spice in food are believed to exhibit curative effects on a wide range of ailments in addition to exhibiting aphrodisiac effect in males according to folklores. Although there is limited information on KB in the literature, MM had been reported to exhibit antineoplastic properties,[7] show promise as an anti-diabetic compound[8] and exhibits anti-plasmodia activity.[9] The presence of phytochemical antioxidants in KB and MM suggests that they may also be useful as chemoprotective agents in biological systems subject to oxidative stress-induced cellular damage.[1011] Such damages induced by oxidative stress have been implicated in the etiology of a plethora of disease conditions.[121314] Arsenic compounds are ubiquitous in nature and released into the environment by anthropogenic activities.[15] Consumption of arsenicals through contaminated water is prevalent in many areas of the world.[16] Arsenicals, like sodium arsenite (SA), are clastogen that trigger chromosomal breakage.[17] SA has been reported to compromises the integrity of the liver of mouse, rat, fish, and goat.[181920] This study investigates the potential toxic effect of KB and MM in rodents. In addition, we also examined the potential chemoprotective effect of KB and MM on SA-induced toxicities using male Wister's rat as a model organism. Observation from this experiments on MM and KB, will contribute to existing knowledge in the areas of functional foods research, by identifying novel roles for existing plants products, application of their biomolecules in therapeutics and advancing health promotion as necessary dietary supplements.

Keayodendron bridelioides and MM are a major constituent of a recreational broth “pepper soup” extensively consumed in Nigeria. KB and MM also find broad base herbal medicinal application, from malaria to a plethora of other ailments. Pepper soup is alleged to have all manner of healing properties in addition to its implied aphrodisiac potentials. Phytochemical identified in KB and MM [Table 1] is known to play important roles in medicinal plants bioactivity. Consequently, their relevance as food and herbal essences that produces physiological action can be validated for wellbeing. However, there is a need for provenance, standardization and cataloging of myriad claims attributed to such herbs and spices, both for current users and posterity.

Flavonoids exhibit antioxidant activity by scavenging or chelating process[323334] on free radicals and metals ions, e.g. copper and iron. This can impair metal absorption from the diet useful in metallo-enzyme function. The flavonoids content of the extracts are thus health promoting[35] at least by reducing lipid peroxidation and chelating excess metals in the diet that may be toxic and deleterious. Overall, phenolic compounds are radical's terminators[36] and can help maintain a reduced cellular environment. The presence of Tannins in the extract may interfere with iron absorption and decreases the cellular iron pool, in excess free iron is implicated in the Fenton process sequel to oxidative stress. In addition, the presence of saponin in the extract has correlations in the practice of herbal medicine where saponins are used as an anti-inflammatory agent.[37] It can be surmised that both KB and MM may act as antioxidants in vivo.

We established a nontoxic dose from KB dose-response study due to paucity of data on KB. While there was significant body weight loss (P < 0.05), all rats treated with different doses of KB survived. In addition, changes in relative liver, weights were not significant compared with control [Table 2].

Keayodendron bridelioides treatment increased serum activities of hepatic transaminases-GGT, ALP, AST and ALT-dose dependently. ALP increased (P < 0.05) across the treated groups (from 50 to 500 mg/kg) compared with control. Increases (P < 0.05) in GGT activity was observed at higher doses of 250 and 500 mg/kg. ALT and AST activities showed little differences compared with the control across the treated groups. Increase in the serum amount of hepatic transaminases maybe attributed to KB hepatotoxicity at very high doses. This can occur in part due to enzyme-induction and metabolism of the extract. Histopathological examination showed no lesions in the liver of the control group [Figure 2]. However, KB treated groups with doses of 250 and 500 mg/kg presented with excessive periportal hepatic necrosis and cellular infiltration by mononuclear cells. KB (100 mg/kg) showed no toxic effect on hepatocytes when compared with the preceding groups. In addition, no visible lesions were observed with the appearance of mild sinusoidal congestion. Groups treated with (50 and 75 mg/kg) showed slight liver toxicity with high cellularity and multiple foci of hepatic necrosis observed. High cellularity can be as a result of increased cell proliferation. Consequently, a dose of 100 mg/kg body weight was chosen for all another experiment. This dose is justified as it showed the lowest form of toxicity, damage and increased cellularity in hepatocyte.

The SOS-chromotest for genotoxicity, qualitatively detects the presence of genotoxic materials in compounds or mixtures of varying type. Our findings indicate that the extract of MM and KB are not genotoxic [Figure 1a and b], providing a clue that they may confer protection from DNA damage by their phenolic components.

There was a general increase in the body weight of animals treated with KB and MM; the observed increase was highest in KB only, least in KB + SA [Table 3]. Relative liver weights were all reduced in treated groups compared to control the group. The increases in body weight could be due to androgenic modulation by the extracts since androgens possess anabolic activity.[38] Consumption of arsenicals through contaminated water is prevalent in many areas of the world. Exposure to SA can be toxic, and our results Table 3] corroborate earlier findings in existing literature. The extracts (100 mg/kg) appear to be hepatoprotective as they decreased hepatic transaminases activities in serum to levels comparable to control rats. KB + SA treatment however increased GGT level in serum to levels higher than SA only treatment. Co-treatment with MM did not alleviate SA-induced toxicity as revealed by GGT and ALT; AST was unexplainably almost two fold higher though ALP was reduced. Increases in serum AST and ALT has been associated with hepatocellular injury and necrotic hepatocytes death[39] respectively. To buttress this observation, MM treatment alone increased (P < 0.05) hepatic transaminase in serum to levels higher than KB induction. Comparatively, it can be taken that to a greater extent MM is more toxic to hepatocytes that KB.

Clastogen induces chromosomal breakage simply described as the microscopically visible changes to chromosomes[40] may results in deletion, addition or rearrangement of sections of chromosomes. These changes may cause mutations that precede the onset of certain diseases. SA can induce chromosomal breakage as such can act as co-mutagen by inhibiting thiol containing enzymes,[41] e.g. DNA ligase consequential in defective DNA replication/repair and recombination.[42] SA-induced micronuclei formation [Table 4] was significantly reduced by MM and KB co-treatment. Alone, MM induced micronuclei formation significantly (P < 0.05) but inhibited SA-induce micronucleus. KB exhibited higher chemoprotective potency alone and against SA micronuclei induction. Making them potentially useful candidates as chemoprotective and medicinal substances in reducing radiation-induced damages worthy of future mechanistic exploration.

Compared with control treatment with extracts reduced sperm count, motility and increased morphological abnormalities in experimental animals. This is suggestive of a modulatory role on the reproductive system. In addition, treatment with SA reflected the same effect [Table 5] albeit to a greater extent decreased sperm motility but increases in count and morphological abnormalities. The volume and ratio of live/dead semen remain unchanged in all groups. MM + SA treatment significantly increased (P < 0.05) sperm cells abnormal morphological characteristics. In line with our finding, impairment of male rat reproductive system treated with SA and sperm count reduction[43] have been reported. MM in folk medicine is believed to be an effective antidote against “sexual impotency” amongst another ailment. This belief is conflicting with our finding and demands further investigation.

Taken together, aqueous extract of (KB and MM) mitigate the effect of SA-induced clastogenicity and are not genotoxic. To a greater extent, KB was more potent in this regard. The extracts appear to be chemoprotective with limited hepatoprotective potentials with selective elevation of hepatic transaminases. Reduction in sperm count, motility and increased sperm abnormalities raising the question as to whether KB and MM are selectively toxic to the reproductive system that warrant further investigations.