Immunotoxicity of Aflatoxin B1 in Rats: Effects on Lymphocytes and the Inflammatory Response in a Chronic Intermittent Dosing Study

Abstract

We investigated the effects of aflatoxin B1 (AFB1) on isolated splenic lymphocytes and the histo-morphologic changes in the spleens and liver of Fisher-344 male rats. Weaned animals were fed chow diets that contained 0, 0.01, 0.04, 0.4, or 1.6 ppm AFB1, using an intermittent dosing regimen (4 weeks on and 4 weeks off AFB1), for 40 weeks. An additional group of animals was fed the 1.6 ppm AFB1 diet continuously. The intermittent dosing regimen was designed to evaluate effects of cumulative dose and exposure for risk assessment comparisons. The percentages of T and B cells were affected as shown by flow cytometric analysis after the dosing cycles. The observed changes appeared to reverse or compensate to some extent after the off cycles. Lymphocytes were stimulated in culture for analysis of the production of IL-2, IL-1, and IL-6. Significantly increased production of IL-1 and IL-6 was seen in the second dosing cycle (12 weeks) and the second "off" cycle (16 weeks) at the higher doses. Inflammatory infiltrates were seen in the liver after eight weeks of continuous and intermittent dosing and were increased in size and number at 12 weeks in both 1.6 ppm dose groups correlating with the peak production of Il-1 and IL-6. We concluded that AFB1 effects on the immune system can be either stimulatory or suppressive dependent on a critical exposure window of dose and time. Immune cells in spleen such as T-lymphocytes and macrophages, both important mediators of inflammatory responses to tissue damage, were affected differently in the continuous and intermittent exposures to AFB1.

Effect of Aflatoxin B1 (AFB1) Residues on the Pathology of Camel Liver

“…The microscopic alterations in liver samples with lower levels were mostly in the form of congestion in the sinusoidal and central vein, hepatocytic steatosis and fatty vacuolations, vacuolar to hydrobic degenerations and haemosidrine pigments. Nearly similar histopathology alterations were previously reported in some studies for aflatoxicosis in other species as these of Colakoglu and Donmez (2012) in Rams, Smith et al (1976) in farm animals, Armbrecht et al (1970) in sheep, Miller et al (1984) in goats, Hinton et al (2003) in rat and Ortatatli et al (2005) in broilers.…”

Impact of Enzymes and Toxins Potentiality of Four Aspergillus Species to Cause Aspergillosis

“…Aflatoxins also show a wide range of immunotoxic effects, they depress phagocytosis, intracellular killing and spontaneous superoxide production of macrophages. Aflatoxin B1 also inhibits the production of the tumor necrosis factor (TNF), interleukin-1 (IL-1) and IL-6 by lipopolysaccharide-stimulated macrophages [62]. Aflatoxins in the lungs were found in all children diagnosed to have pneumonia, irrespective of the presence of kwashiorkor.…”

Short communication: Inhibitory effects of dietary aflatoxin B1 on cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens

“…The inhibitory effects of AFB 1 on cytokines expression and T-cell subsets have been demonstrated in various studies. The dietary AFB 1 can induce inhibitory effects on interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-6 (IL-6) production in rats' splenocytes (Hinton et al, 2003). There is also a decrease in contents of serum IL-2 and interferon gamma (IFN-γ) in broilers exposed to AFB 1 (Chen et al,2 observed reduced percentages of CD3+, CD3+CD4+ and CD3+CD8+ T-cells in the spleen of broilers administered AFB 1 .…”