The neurological effects of Solanum dimidiatum in mice

Abstract

The purpose of this investigation was to examine the toxic properties of Solarium dimidiatum and to establish how the toxicant acts upon the nervous system, causing the "Crazy Cow Syndrome." To obtain this information, mice were chosen as the experimental model. Alkaloids contained in this plant are thought to be the toxic principle. Therefore, quantitation of the total glycoalkaloid content was essential. Extensive chemical analysis of the plant was done. Hydrolysis, both in vitro and in vivo, was performed and the compounds isolated and identified. Acute intraperitoneal pilot studies with the isolates were done to ascertain which ones, if any, were toxic. Two ninety-day chronicity studies were performed on the mice, one with a crude extract of the plant and one with pure suspected toxin. In both studies, the mice were observed for indications of neurologic dysfunction. The acetylcholinesterase inhibitory potential of S. dimidiatum was also explored to discern if this contributes to the demise of the animal. An ancillary objective was to elucidate any hepatoxicity since diosgenin, an known hepatotoxin, was isolated. The mice dosed with the crude extract (medium and high dosage groups) of Solanum dimidiatum lost a significant amount of weight, suggesting intoxication from the glycoalkaloid. Those given the aglycone, however, did not exhibit gastrointestinal injury. The high and medium dose groups in both chronicity studies had reduced acetylcholinesterase activity, but apparently not severe enough to cause death or the neurologic deficit in question. Neither study resulted in a significant difference in the mice's ability to complete the ataxia assay. The high and medium dose groups in the second chronicity study with solanidine displayed aberrant behavior. This response, which included nervousness, extreme agitation, and episodes of aggressiveness, was dose related. Histopathology of the cerebellums and spinal cords revealed no lesions. In vivo and in vitro hydrolyzed compounds were isolated and identified. Oddly enough, the two systems did not provide identical compounds although the parent compounds were the same, namely the glycoalkaloids solanine and chaconine. Both hydrolysis systems discerned the presence of sapogenins that are potentially toxic.