Effects of alloxan upon goldfish ( Carassius auratus L.)

Abstract

Attempts to clarify the role of the islets of Langerhans in the control of serum glucose levels in teleosts have not been entirely successful. In order to determine precisely alloxan-induced alterations in the goldfish ( Carassius auratus L.), the environmental variables and serum glucose methodology were standardized and the animals studied in regard to both dose and time. The cytological and physiological responses in certain endocrine and nonendocrine tissues were evaluated temporally at the alloxan dose of 600 mg/kg. Of the 1,563 fish used, 442 were sectioned serially at 3 μ, stained with AF-trichrome, and studied microscopically. The liver glycogen was studied histochemically. Serum glucose levels of all fish were determined in duplicate 10-μl serum samples by the glucose oxidase procedure. Continuous alloxan immersion (0.02 to 0.09%) of goldfish ( Carassius auratus L.) maintains hyperglycemia; return to fresh water reduces serum glucose levels to normal in 3 days. Alloxan (200–400 mg/kg), 24 hr postinjection, ip, produces slight hyperglycemia; 450–900 mg/kg alloxan evokes severe hyperglycemia. The alloxan LD 50 7 day is 600 to 700 mg/kg. Saline (0.58%) injection produces a rapid transient hyperglycemia and return to the normal range in 4 hr. Coneurrent adrenal alterations and liver glycogen depletion indicate this transient hyperglycemia to be a “stress” response. Study of the fish injected with alloxan reveals a triphasic serum response similar to that occurring in mammals. The initial hyperglycemia and hypoglycemia appear to results from “stress” and release of insulin from beta cells, respectively. The prolonged hyperglycemia following hypoglycemia is attributed to beta cell destruction, but other factors (release of glucagon and liver and kidney damage) also play an important role. Persistent adrenal hypertrophy suggests that alloxan produces a continual state of “stress” during the period of study. Recovery of normal serum glucose levels in the surviving animals results from beta cell recuperation and restoration of normal liver and kidney structure. The alloxan diabetic syndrome in teleosts may be better understood only with consideration of the toxic effects of alloxan.