Effect of lead exposure and nutritional iron-deficiency on immune response: A vaccine challenge study in rats.

The prevalence of iron (Fe) deficiency and subclinical lead (Pb) toxicity is high in developing countries like India, and information on their potential additive effects on immune responses is scant. The current study assessed immune parameters in dual Pb-exposed\Fe-deficient weanling SD rats. Rats were fed a control (CD) or Fe-deficient (ID) diet for 4 weeks and then evaluated for hemoglobin (Hb) and serum Fe status. Then, half the rats in each group began to receive daily oral Pb exposure (25 mg/4 ml/kg BW; gavage) or vehicle for a further 4 weeks (while maintained on original respective diets). After the 4-weeks of dosing, rats were assessed for Hb and serum Fe, and for blood lead level (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity. At this point, half the rats in each group (now n = 8) were then vaccinated with tetanus toxoid (TT), and then two boosters at 2-week intervals. All the time, rats stayed on their original respective diets along with exposure to Pb on alternate days. At 2 weeks after the final booster, rats were euthanized and blood collected to assess total/specific IgG and IgM levels; mucosal (intestinal) IgA levels were also determined. Spleens were taken to assess CD4+ and CD8+ cell levels and for ex vivo measures of splenocyte proliferation/TH1 and TH2 cytokine formation. The results indicated significant lowering of Hb and serum Fe levels in ID rats and increased blood Pb and decreased ALAD activity in all Pb-exposed rats. Fe-deficiency alone induced significant increases in ALAD activity, but only in an absence of Pb. While there was no impact of any regimen on total or TT-specific IgG, significant decreases in mucosal IgA and TT-specific IgM were seen in ID-fed Pb-exposed rats. CD4+ cell levels were not impacted by treatment; CD8+ levels were increased in all ID/Pb-exposed rats. Ex-vivo splenocyte proliferation was significantly higher among vaccinated rats, as well as ID-fed Pb-exposed unvaccinated rats. Cytokine formation in all cases was highly variable. The results suggest that Fe deficiency compromised cell-mediated, mucosal, and/or humoral immune response-related endpoints and that Pb exposure during the deficiency further impacted these outcomes.

Zinc deficient diet exacerbates the testicular and epididymal damage in type 2 diabetic rat: Studies on oxidative stress-related mechanisms.

Zinc (Zn) is one of the most important trace elements in the body and is required for insulin secretion and release. Zn is also required for the growth and development of the reproductive system. Alteration in the Zn levels can cause moderate to severe damage to various organs, including the reproductive system. Most of type 2 diabetic patients have altered Zn levels/signaling. So, here we investigated the role of Zn-deficient diet (ZDD) in type 2 diabetes. Type 2 diabetes in the rat was induced by the combination of high-fat diet (HFD) and a single low dose of streptozotocin (STZ, 35 mg/kg, i.p.). Control animals were fed normal pellet diet throughout the study, while ZDD was given for four consecutive weeks to the diabetic rats, which were earlier kept on HFD for 16 weeks. The present findings showed that ZDD further decreased the serum Zn, plasma insulin and serum testosterone levels, whereas it increased cholesterol, triglycerides, BUN, %HbA1c in diabetic rats. Oxidative stress in testes was increased by ZDD as evidenced by decreased glutathione, catalase and SOD1 levels. ZDD-induced several abnormalities in sperm head morphology, altered sperm decondensation, sperm chromatin and protamine content, along with significant histopathological alterations in testes and epididymis. Further, ZDD altered protein levels of MT, MTF-1, Keap1, Nrf2, Nf-κB, GPX4 and GPX5 levels in the testes and epididymis of diabetic rat. The present results demonstrated that dietary Zn deficiency could exacerbate type 2 diabetes-induced germ cell damage.

The effect of lead (Pb) exposure and iron (Fe) deficiency on intestinal lactobacilli, E. coli and yeast: A study in experimental rats.

OBJECTIVE: The current study investigated the additive effect of oral lead (Pb) exposure and dietary iron (Fe) deficiency on intestinal lactobacilli, E. coli, and yeast in SD rats. METHODS: Weanling rats were fed on control diet (CD) or iron deficient diet (ID) for 4 weeks, followed by oral Pb exposure for another 4 weeks. Lead exposure was withdrawn for 2 weeks, and then resumed after 2 weeks. Blood samples were collected to determine haemoglobin (Hb), serum iron, blood Pb and δ-Aminolevulenic acid dehydratase (ALAD) activity. Fecal samples were collected to enumerate the lactobacilli, E. coli and yeast population on selective agar media and determine Pb levels. RESULTS: Hb and serum Fe levels decreased significantly in iron deficient rats. Pb exposed rats had a significant increase in blood Pb levels and decreased ALAD activity. The lactobacilli population was significantly decreased (p<0.05) in ID rats compared to the CD group. Further, a significant decrease in the lactobacilli population was observed in Pb exposed rats irrespective of the dietary regimen. Upon withdrawal of Pb exposure, lactobacilli increased significantly in both the CD+Pb and ID+Pb groups, whereas re-exposure to Pb decreased lactobacilli population. The E. coli and yeast populations were inconsistent among both the ID and Pb exposed rats compared to controls. Fecal Pb levels increased significantly in Pb exposed rats irrespective of diet. CONCLUSION: An additive effect of dietary Fe deficiency and oral Pb exposure resulted in greater reductions in the intestinal lactobacilli population compared to either treatment alone. In addition, transient withdrawal of Pb exposure led to improved lactobacilli population irrespective of Fe status.