Vol 43 # 3 September 2011 - Kma.org.kw

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202 Characterization of Acrylamide Mediated Testicular Toxicity in Rat: Light and Electron ... September 2011 Fig. 8: (A) Part of seminiferous tubule from control rat testis showing many normal spermatogenetic (arrows) and Sertoli cells (S) x 1100, (B) Control rat testis showing Sertoli cell with prominent nucleolus (long arrow) and two characteristic bodies near it (small arrow) x 4600, Insert showing apical cleft of the nucleus (arrow) and mitochondria (M) in the cytoplasm x 10,500, (C) rat testes treated with 45 mg/kg AA showing degenerated spermatogonia (sg) with large lipid droplet (LD),degenerated peritubular myoid cell (MC) and vacuole (V) at the basal part of the tubule x 3400. The insert showing widening of the intercellular junctions (arrow) of the two adjacent germ cells x 5800, (D) rat testes treated with 45 mg/kg AA showing degenerated Sertoli cell nucleus (N) with condensed chromatin and shrunken nucleolus (arrow). Cytoplasmic lipid droplets (small arrow), widening of tight junctions between Sertoli cell and the surrounding spermatocytes (star) were observed. Detachment of Sertoli cell from the basal lamina (double head arrow) was also observed x 7900. The insert showing spermatid (arrow) phagocytozed by the Sertoli cell x 7900. Transmission electron microscope spermatid showed normal shape, number and arrangements of outer dense fibers (ODF) through the middle and principal piece of its tail. However, partial dissolution of fibrous sheath in the principal piece was frequently observed (Fig. 9 D). Leydig cells showed clear atrophy after AA treatment (Fig. 9 A and B). DISCUSSION In this study, testicular toxicity of AA was investigated by examining the influence of this compound on body weight changes, testis and epididymal weight, sperm count and morphology and histopathological changes in rat testis and epididymis. Rats gavaged with AA at doses of 45 or 60 mg/kg/ day for five days showed a significant reduction in body weight. A reduction in epididymal sperm count was observed in the group treated with 60 mg/kg AA. Abnormal epididymal sperm morphology and abnormal histopathological findings were noted in the testis of all treated rats. These dose response changes provided the initial characterization of AA induced testicular toxicity in rats. Gross observational and behavioural changes and neurotoxicity observed on rats treated with AA at doses of 45 and 60 mg/kg were entirely consistent with the previous study conducted by Hashimoto et al [8] who treated mice with 0.2 to 0.5 of the LD50 of AA (1.5 mmol/kg equivalent to 106.6 mg/kg) twice weekly by oral gavage for 8-10 weeks. Tyl et al and Lopachin [17,18] have also reported this phenomenon in rats. It must be highlighted that no clear mechanism underlying AA neurotoxicity has yet been uncovered, although several possible mechanisms have been suggested. These include inhibition of kinesin-based
September 2011 KUWAIT MEDICAL JOURNAL 203 Fig. 9: (A) Leydig cells of the control rat testis appear normal x 620. (B) Leydig cell of 45 mg/kg AA treated rat appear atrophied and few in number x 620, (C) transverse and longitudinal sections in the axoneme of developing spermatids from control rat showing mitochondria (M) surrounding the middle piece of the tail, also the annulus (AN) between middle and principal piece x 7900. The insert showing transverse sections through the principal piece of spermatids. Note complete dissolution (arrow) of one circumferential rib in the principal piece x 34,000. (D) spermatid of rat treated with 45 mg/kg AA showing longitudinal section of the principal piece of a spermatid. Note the fibrous sheath (arrow) x 64,000. The insert showing transverse section of the principal piece of spermatid, with normal shape ODF. Note partial dissolution started to occur above ODF number one x 92,000. Transmission electron microscope fast axonal transport by AA [19] , induction of synaptic dysfunction by AA[ 20] , or a central mechanism operating through inhibition of brain GST and a decrease in brain dopamine receptors [21] . Additionally, it should be noted that hind limb dysfunction is one of the factors that negatively influences or disrupts the copulatory behavior of male rats [14] . Similarly, in a study conducted by Yang et al [6] , there was a significant reduction in rat body weights at doses of 45 and 60 mg/kg/day compared to the control group, following the oral gavage of AA for five consecutive days. In a study reported by Sakamoto et al [24] , in which prepubertal and adult male mice received a single oral dose of 100 or 150 mg/kg of AA, the mice showed a significant reduction in body weight for three and five days, respectively, following the treatment. In contrast to the above studies, many other investigators have reported that AA has no influence on the body weight of treated animals [8,22,23] . It is unclear at present why these differences should exist in the influence of AA on body weight. However, it might be a function of the dose or the rat strain used. The interpretation for this body weight loss following AA treatment may be due to loss of appetite by the treated animals, leading to decreased food intake and consequent decline in weight. In the current study, a significant increase in testis to body weight ratio was detected among groups treated with 15 mg, 45 mg and 60 mg/kg. This result is in agreement with finding of Sakamoto et al [24] in adult mice following a single oral dose of AA (150 mg/kg). In that case, the absolute testicular weight was not affected, but the testes to body weight ratio was increased significantly. This was in contrast to several previous
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Vol 43 # 3 September 2011 - Kma.org.kw

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