Large-scale staple food fortification as a complementary strategy to address vitamin and mineral vulnerabilities in India: A critical review.

The slow improvement in micronutrient malnutrition globally and in India warrants a need for scaling-up scientifically proven, cost-effective public health interventions. The present review discusses the potential of staple food fortification as a complementary strategy to tackle micronutrient deficiencies, while addressing the current concerns raised regarding its implementation. The review indicates the below par status of current strategies like dietary diversity and supplementation to address multiple micronutrients deficiencies in India and the need for complementary strategies to tackle this problem. Based on systematic reviews and meta-analysis, global and national evidence has identified staple food fortification as a proven and recognized cost-effective solution to address micronutrient deficiencies. The Government of India has shown a strong leadership to promote this proven intervention. Further, the paper addresses the concern that large-scale staple food fortification (LSFF) may lead to excessive nutrient intakes when delivered together with other interventions, e.g., supplementation, dietary diversity, among the same populations. A key message that emerges from this review is that LSFF is safe with current dietary intake and deficiencies and low coverage of other interventions. Given the current situation of food and nutrition insecurity which the COVID-19 pandemic has further exacerbated, and the critical role that nutrition plays in building immunity, it is even more important that health and nutrition of the population, especially vulnerable age groups, is not only safeguarded but also strengthened. LSFF should be implemented without any further delay to reach the most vulnerable segments of the population to reduce the dietary nutrient gap and prevent micronutrient deficiencies. Effective monitoring and regular dietary surveys will help ensure these interventions are being deployed correctly.

Antemortem and postmortem examinations of the cattle calf naturally infected with Mycobacterium avium subsp. paratuberculosis.

A male cattle calf was detected as subclinically and naturally infected with Mycobacterium avium subspecies paratuberculosis (MAP) by a series of antemortem and postmortem tests. The MAP infection was identified by strong antibody and cell-mediated immune (CMI) response by a commercial ELISA kit and an intradermal Johnin test, respectively, in the initial antemortem examination. The antemortem status of the calf was further confirmed by MAP-specific interferon gamma (IFN-γ) response. For detection of IFN-γ response, MAP-specific IFN-γ release assays (IGRAs): (a) immuno capture ELISA (IC-ELISA) and (b) ELISPOT was employed. In addition, the presence of intracellular cytokine IFN-γ was detected by flow cytometry. For all cytokine assays, MAP-specific recombinant antigens HSP65 and 35 kDa were employed to overcome the poor sensitivity and specificity resulting from the use of Johnin, the crude protein purified derivative of MAP. Postmortem examination of the MAP-infected/suspected cattle calf did not reveal any pathognomonic gross lesions in the gastro-intestinal tract. Histopathological examination of multiple organs showed the presence of epithelioid cells/macrophages and edematous lesions in the mesenteric lymph nodes suggestive of MAP; however, no granulomas were observed in the intestinal tract. The necropsy samples of rectum and mesenteric lymph nodes were positive for isolation of MAP by culture in the BACTEC™ MGIT™ 960 system, and acid fast bacilli were demonstrated by fluorescence microscopy confirming the infection. Due to differential and complex expression patterns of MAP antigens reported in literature, a combination of assays such as those based on IGRAs and antibody detection is essential. Therefore, the current experimental evidence confirms the efficacy of the approach adopted. However, further studies will be needed to understand the optimal combination MAP-specific antigens for use in IGRAs or antibody assays that can be used for detecting MAP infection in every stage of the disease.

Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta).

BACKGROUND & OBJECTIVES: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 µg)] and combination rabies vaccine [CRV (100 µg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. METHODS: As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. RESULTS: In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28 th day. INTERPRETATION & CONCLUSIONS: The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.

Effect of maternal undernutrition on human foetal pancreas morphology in second trimester of pregnancy.

BACKGROUND & OBJECTIVES: Maternal undernutrition and hyperglycaemia during pregnancy, as well as foetal undernutrition affecting the development of foetal endocrine pancreas structure and function, especially that of ß-cells is well known. This study was undertaken to look into the changes in pancreatic islets morphology of aborted normal human foetuses (16-20 wk old) of undernourished and adequately nourished mothers. METHODS: Foetuses were collected over a 24 month period from medically terminated pregnancies of six undernourished mothers (BMI <18.5 kg/m² and eight adequately nourished mothers (BMI >18.5 kg/m². The sections were stained with haematoxylin & eosin as well as Masson trichrome for morphometric estimates such as islet count, area, volume, etc. and immunohistochemistry analysis of ß-cells for insulin presence was done. RESULTS: Significant correlations between maternal and foetal parameters were seen. However, there were no statistically significant differences in the number, size or density and beta cell counts of the pancreas among foetal pancreas of mothers with BMI <18.5 and >18.5 kg/m². INTERPRETATION & CONCLUSIONS: Our findings indicate that nutritional status of the mother may not have profound influence on the morphology of beta cells of foetal pancreas in second trimester of pregnancy. Further studies need to be done to confirm these findings.

Aflatoxin contamination in stored rice variety PAU 201 collected from Punjab, India.

BACKGROUND & OBJECTIVES: The present study was carried out on stored rice variety PAU 201 in Punjab that was not permitted for milling and public distribution due to the presence of damaged grains at levels exceeding the regulatory limits of 4.75 per cent. The aim of the study was to determine fungal and aflatoxin contamination in the rice samples to assess hazard from the presence of damaged grains. Presence of iron in discoloured rice grains was also assessed. METHODS: Stored samples of paddy of PAU 201 rice variety were collected from six districts of Punjab, milled and analysed for presence of fungal and aflatoxin contamination. Scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and Prussian blue staining was used to determine fungal spores and presence of iron, respectively. RESULTS: Aflatoxin analysis of rice samples indicated that none exceeded the Food Safety and Standards (Contaminants, Toxins and Residues) Regulations, 2011 tolerance limit of 30 µg/kg and majority of the samples had levels <15 µg/kg. The proportion of damaged grains exceeding the limit of 5 per cent was observed in 85.7 per cent of the samples. SEM and Prussian blue staining and EDX analysis of black tipped and pin point damaged rice grains did not show presence of fungal structures and presence of iron. INTERPRETATION & CONCLUSIONS: The results of the study indicated that the stored rice samples did not pose any health concern with respect to aflatoxin contamination as per the criteria laid down by the Food Safety and Standards Authority of India.

Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: a randomized, double-blind study.

The purpose of this study was to evaluate the effectiveness of lactobacilli on vaginal health and proinflammatory cytokines. Sixty-seven patients with bacterial vaginosis (BV), 50 with intermediate flora and 42 with normal vaginal flora were enrolled in this double-blind study. The subjects were randomized to receive probiotic lactobacilli vaginal tablets (L. brevis CD2, L. salivarius subsp. salicinius, L. plantarum) or the vaginal pH tablet (active comparator). Cervico-vaginal lavage was collected to measure the concentrations of IL-1ß, TNFα and IL-6 by ELISA. Neutral sphingomyelinase activity was also quantified in both arms before and after treatment. The probiotic vaginal tablet was well tolerated and no side effects were reported. The study demonstrated a cure rate of nearly 80 %; i.e., 32 % of the women could restore normal vaginal flora and 47 % had improved Nugent score, whereas 20 % of the subjects did not clear BV in the first follow-up (after 8 days treatment). The pH tablet containing pH lowering compounds induced resolution of BV and restoration of normal vaginal flora in 74 % and 26 %, respectively. The lactobacilli tablet was found to be better than the pH tablet in preventing BV in healthy subjects. A significant reduction in IL-1ß and IL-6 vaginal cytokines was observed after treatment with lactobacilli, while the active comparator did not have any effect on local proinflammatory cytokines. Vaginal neutral sphingomyelinase activity was not modified in either group. Vaginal tablets containing lactobacilli can cure BV and reduce vaginal inflammatory response.

Constantly evolving safety assessment protocols for GM foods.

he introduction of GM foods has led to the evolution of a food safety assessment paradigm that establishes safety of the GM food relative to its conventional counterpart. The GM foods currently approved and marketed in several countries have undergone extensive safety testing under a structured safety assessment framework evolved by international organizations like FAO, WHO, Codex and OECD. The major elements of safety assessment include molecular characterization of inserted genes and stability of the trait, toxicity and allergenicity potential of the expressed substances, compositional analysis, potential for gene transfer to gut microflora and unintentional effects of the genetic modification. As more number and type of food crops are being brought under the genetic modification regime, the adequacy of existing safety assessment protocols for establishing safety of these foods has been questioned. Such crops comprise GM crops with higher agronomic vigour, nutritional or health benefit/ by modification of plant metabolic pathways and those expressing bioactive substances and pharmaceuticals. The safety assessment challenges of these foods are the potential of the methods to detect unintentional effects with higher sensitivity and rigor. Development of databases on food compositions, toxicants and allergens is currently seen as an important aid to development of safety protocols. With the changing global trends in genetic modification technology future challenge would be to develop GM crops with minimum amount of inserted foreign DNA so as to reduce the burden of complex safety assessments while ensuring safety and utility of the technology.

Evidence for a sequential transfer of iron amongst ferritin, transferrin and transferrin receptor during duodenal absorption of iron in rat and human.

AIM: To elucidate the sequential transfer of iron amongst ferritin, transferrin and transferrin receptor under various iron status conditions. METHODS: Incorporation of 59Fe into mucosal and luminal proteins was carried out in control WKY rats. The sequential transfer of iron amongst ferritin, transferrin and transferrin receptor was carried out in iron deficient, control and iron overloaded rats. The duodenal proteins were subjected to immunoprecipitation and quantitation by specific ELISA and in situ localization by microautoradiography and immunohistochemistry in tandem duodenal sections. Human duodenal biopsy (n = 36) collected from subjects with differing iron status were also stained for these proteins. RESULTS: Ferritin was identified as the major protein that incorporated iron in a time-dependent manner in the duodenal mucosa. The concentration of mucosal ferritin was significantly higher in the iron excess group compared to control, iron deficient groups (731.5 +/- 191.96 vs 308.3 +/- 123.36, 731.5 +/- 191.96 vs 256.0 +/- 1.19, P < 0.005), while that of luminal transferrin which was significantly higher than the mucosal did not differ among the groups (10.9 +/- 7.6 vs 0.87 +/- 0.79, 11.1 +/- 10.3 vs 0.80 +/- 1.20, 6.8 +/- 4.7 vs 0.61 +/- 0.63, P < 0.001). In situ grading of proteins and iron, and their superimposition, suggested the occurrence of a sequential transfer of iron. This was demonstrated to occur through the initial binding of iron to luminal transferrin then to absorptive cell surface transferrin receptors. The staining intensity of these proteins varied according to the iron nutrition in humans, with intense staining of transferrin receptor observed in iron deficient subjects. CONCLUSION: It is concluded that the intestine takes up iron through a sequential transfer involving interaction of luminal transferrin, transferrin-transferrin receptor and ferritin.

Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.

The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.

Vitamin A supplementation induces adipose tissue loss through apoptosis in lean but not in obese rats of the WNIN/Ob strain.

Vitamin A is a known regulator of adipose tissue growth. In this paper, we report the possible role of dietary vitamin A supplementation in the regulation of adipose tissue mass, using a novel obese rat model of the WNIN/Ob strain developed at the National Centre for Laboratory Animal Sciences of the National Institute of Nutrition, India. Twenty-four male lean and obese rats of the WNIN/Ob strain were broadly divided into two groups at 7 months of age; each group was subdivided into two subgroups consisting of six lean and six obese rats and they were given diets containing either 2.6 mg or 129 mg vitamin A/kg diet for 2 months. Feeding a high but non-toxic dose of vitamin A (129 mg/kg diet) resulted in a significant reduction in the adiposity index and retroperitoneal white adipose tissue (RPWAT) weight in obese rats while a marginal reduction was observed in lean rats. Further, this treatment resulted in a significantly increased RPWAT apoptotic index and Bax protein expression and a decreased expression of Bcl2 in the lean rats. However, no such changes were observed in the RPWAT of the obese rats subjected to identical treatment. Thus, our data suggests that chronic dietary vitamin A supplementation at a high dose effectively regulates adipose tissue mass both in the lean and obese phenotypes of the WNIN/Ob rat strain, perhaps through different mechanisms.

Serum transferrin receptor in children with respiratory infections.

OBJECTIVE: To study the effect of infection on iron status in children suffering from acute, mild or severe respiratory infections and to determine the nature of anemia in infection using serum transferrin receptor (sTfR) levels. DESIGN: Forty-three children aged between 3 and 5 y with no evidence of infection and receiving iron supplements in the preceding 100 days served as controls. Twenty-one children with mild upper respiratory infection and 94 children hospitalized for acute pneumonia constituted the experimental group. Hemoglobin (Hb), sTfR and serum ferritin were estimated in all the children at the time of diagnosis and again on the 15th and 30th days after the infection in those who were available for follow-up. RESULTS: Mean (95% CI) sTfR was 6.08 (5.1-7.1) mg/l in healthy non-anemic children. Upper respiratory infection had no impact on Hb or sTfR but it significantly elevated serum ferritin levels. Eighty-three percent of the children with pneumonia had Hb less than 110 g/l at the time of diagnosis and had elevated mean sTfR, 18.0 (15.7-20.3) mg/l. There was a decline in mean sTfR by the 15th day of infection to 14.3 (11.3-17.4) mg/l with further rise to 22.9 (13.0-31.9) mg/l by 30 days. Serum ferritin was significantly elevated at the time of diagnosis (85.9; 71.1-100.8 micro g/l) as well as at 15 days (89.1; 68-110.1 micro g/l) with a decline by 30 days. CONCLUSIONS: Severe lower respiratory infection exaggerates iron-deficient erythropoiesis by blocking release of iron from the storage pools. sTfR may not be a sensitive and specific tool of assessing true iron status of children exposed to severe infections.

Effect of long-term dietary manipulation on the aggregation of rat lens crystallins: role of alpha-crystallin chaperone function.

PURPOSE: To investigate the effect of food, protein, and vitamin restriction on the susceptibility of lens crystallins to aggregation and chaperone activity of alpha-crystallin. METHODS: Thirty day old Wistar/NIN rats were maintained on regular rodent diet (C), 50% food restriction (FR), 75% protein restriction (PR), and 50% vitamin restriction (VR) diet for 20 weeks. At the end, alpha-, beta-, and gamma-crystallins were isolated from the lenses of these animals and subjected to in vitro aggregation induced by oxidation, UV irradiation and heat. Aggregation and chaperone activity was assessed by light scattering methods. RESULTS: Dietary restriction has been shown to extend the mean and maximum life span and retard age-related diseases, including cataract. In this study, we demonstrate that while beta- and gamma-crystallins isolated from FR and PR groups were less susceptible to in vitro induced aggregation, beta- and gamma-crystallins from the VR group were more susceptible, compared to controls. Alpha-crystallin from any of the groups did not shown a considerable amount of aggregation. On the other hand, the chaperone activity of alpha-crystallin from FR and PR groups was not significantly different from controls. However, alpha-crystallin from the VR group demonstrated substantially higher chaperone activity than controls. CONCLUSIONS: These results indicate that while food and protein restriction appear to lower the susceptibility of beta- and gamma-crystallins towards aggregation, vitamin restriction tends to increase the aggregation. Chaperone activity of alpha-crystallin is affected (improved) by only vitamin restriction.

Effects of dietary alpha-linolenic acid from blended oils on biochemical indices of coronary heart disease in Indians.

PUFA of the n-6 and n-3 series have beneficial effects on key risk factors of coronary heart disease (CHD). Our earlier studies on the intake of FA and on the FA composition of plasma and platelet phospholipids suggested the need to improve the n-3 PUFA nutritional status in the Indian population. The present long-term study was conducted on 80 middle-aged Indian subjects (40 men and 40 women) using the subjects' own home-prepared diets to evaluate the effects of dietary n-3 PUFA on biochemical indices of CHD risk. Substitution of Blend G (equal proportions of groundnut and canola oils) for groundnut oil or substitution of Blend S (equal proportions of sunflower and canola oils) for sunflower oil increased alpha-linolenic acid (ALNA) fourfold and decreased the linoleic acid (LA)/ALNA ratio from 35 to 6 and 65 to 9, respectively. Twelve subjects (six men and six women) who received Blend G were switched back to groundnut oil and were administered 0.3 g daily of long-chain (LC) n-3 PUFA from fish oil. At the end of the trial period for both blends in both sexes, plasma lipid and apolipoprotein levels had not changed, and ADP-induced aggregation had decreased. In plasma and platelet phospholipids, LA as well as LCn-3 PUFA had increased, suggesting competition between LA and ALNA for metabolism into the respective LC-PUFA. Fish oil supplementation increased LCn-3 PUFA in plasma and platelet phospholipids, decreased ADP-induced platelet aggregation, and increased plasma cholesterol. On the basis of the increased LCn-3 PUFA in plasma phospholipids, it was calculated that 0.75% energy (en%) (2.2 g) ALNA (from vegetable oils) may be required to increase LCn-3 PUFA to about the same extent as 0.1 en% (0.3 g) LCn-3 PUFA (from fish oils). Since both n-6 and n-3 PUFA play a critical role in fetal growth and development and in the programming of diet-related chronic diseases in adults, an improvement in the n-3 PUFA nutritional status in cereal-based diets through long-term use of cooking oils containing 25-40% LA and 4% ALNA may contribute to the prevention of CHD in Indians.

Studies on skeletal muscle biopsies in endemic skeletal fluorosis.

Neurological manifestations of skeletal fluorosis have been attributed to compressive radiculomyelopathy. Experimental fluorosis has shown evidence of myopathic changes. Data on human muscle pathology is very scanty. This study included 22 patients with established osteofluorosis. 16 of them showed only EMG changes of neurogenic muscle disease. Histochemistry and histopathology of muscle biopsies showed features of muscle atrophy, evidenced by 'type I' atrophy and 'type I' grouping. No myopathic changes were observed. It may be concluded that the primary changes are related to the nerve, with muscle being affected secondarily. There was no evidence of any primary muscle pathology due to fluorosis.

Retardation of experimental tumorigenesis and reduction in DNA adducts by turmeric and curcumin.

Turmeric and its active principle curcumin have been extensively investigated for their antimutagenic and antioxidant effects in bacterial and animal systems. Because oral cancers are common in India, an experimental model of 7,12-dimethylbenzanthracene-induced buccal pouch tumors in Syrian Golden hamsters was used to evaluate the tumor retardation effects of turmeric and curcumin. Turmeric and/or curcumin was administered in the diet and/or applied locally for 14 weeks along with 7,12-dimethylbenzanthracene. After the experimental period, the animals were sacrificed and oral pouches were examined for tumor number and size. DNA adducts were estimated by 32P postlabel assay in the cheek pouches. Neoplastic changes were graded by histopathology. The results of the study suggest that turmeric or curcumin in the diet and/or applied locally significantly reduced DNA adducts at the target site. Tumor number and tumor burden were significantly lower (p < 0.05) in the animals that received turmeric in the diet and applied locally. The histopathological examinations suggested that the neoplastic grading was least in the animals fed or painted with curcumin (p < 0.05). The current study demonstrates that turmeric or curcumin administered in the diet or applied as paint may have a plausible chemopreventive effect on oral precancerous lesions.

The protective effects of eugenol on carbon tetrachloride induced hepatotoxicity in rats.

Our earlier studies in vitro have shown that eugenol inhibits liver microsomal monooxygenase activities and carbon tetrachloride (CCl4)-induced lipid peroxidation (Free Rad. Res. 20, 253-266, 1994). The objective of the present investigation was to study the in vivo protective effect of eugenol against CCl4 toxicity. Eugenol (5 or 25 mg/kg body wt) given orally for 3 consecutive days did not alter the levels of serum glutamic oxalacetic transaminase (SGOT), microsomal enzymes such as cytochrome P450 reductase, glucose-6-phosphatase (G-6-Pase) xenobiotic-metabolizing enzymes (aminopyrine-N-demethylase, N-nitrosodimethylamine-demethylase and ethoxyresorufin-O-deethylase) and liver histology. Doses of eugenol (5 or 25 mg/kg) administered intragastrically to each rat on three consecutive days i.e. 48 hr, 24 hr and 30 min before a single oral dose of CCl4 (2.5 ml/kg body wt) prevented the rise in SGOT level without appreciable improvement in morphological changes in liver. Eugenol pretreatment also did not influence the decrease in microsomal cytochrome P450 content, G-6-Pase and xenobiotic-metabolizing enzymes brought about by CCl4. Since eugenol is metabolized and cleared rapidly from the body, the dose schedule was modified in another experiment. Eugenol (0.2, 1.0, 5.0 or 25 mg/kg) when given thrice orally i.e. prior to (-1 hr) along with (0 hr) and after (+3 hr) the i.p. administration of CCl4 (0.4 ml/kg) prevented significantly the rise in SGOT activity as well as liver necrosis. The protective effect was more evident at 1 mg and 5 mg eugenol doses. However, the decrease in microsomal G-6-Pase activity by CCl4 treatment was not prevented by eugenol suggesting that the damage to endoplasmic reticulum is not protected. The protective effect of eugenol against CCl4 induced hepatotoxicity is more evident when it is given concurrently or soon after rather than much before CCl4 treatment.

Iodine metabolism in response to goitrogen induced altered thyroid status under conditions of moderate and high intake of iodine.

Metabolic experiments in rats were undertaken to relate excretory pattern of iodine and thiocyanate, with thyroid weight and the circulating levels of thyroxine, in response to moderate and high intake of iodine and under conditions of goitrogen induced altered thyroid status. On a moderate intake of iodine (by depriving diet of KI) 25 mg of thiocyanate or substitution of 1/3rd proportion of casein based diet with dry cabbage, could significantly reduce plasma thyroxine level by 60 days. Neither body weight nor the weights of liver, kidney, heart or spleen were affected due to exposure to goitrogens. A significant increase in thyroid weight as well as higher excretion of iodine and thiocyanate were evident in goitrogen-fed rats. Presence of high amounts of KI, to a certain extent, offered protection from adverse effects of the goitrogens. Semi quantitative assessment of thyroid, indicated hypofunctioning of thyroid with follicular hyperplasia in thiocyanate fed rats. These alterations were of moderate degree in response to cabbage feeding. These results emphasize that, moderate intake of iodine, adequate to meet iodine requirement, may not ensure normal functioning of thyroid in the presence of goitrogens.

Effect of iron deficiency on DMH-induced gastrointestinal tract tumors and occurrence of hepatocyte abnormalities in Fischer rats.

The relationship between iron deficiency and carcinogenesis was studied using the carcinogen dimethylhydrazine to induce gastrointestinal tumors in Fischer 344 control and iron-deficient rats. Dimethylhydrazine (30 mg/body wt) was administered by gastric intubation 10 times over nine weeks. After 32 weeks, rats were sacrificed, and tumor incidence was assessed. The overall incidence of gastrointestinal tract tumors (colonic and duodenal) was higher in the iron-deficient (66%) than in the control group (46%). Whereas the incidence of colonic tumors was identical in control and iron-deficient groups, the duodenal tumor incidence was significantly elevated in iron deficiency. Five of 15 rats, i.e., 33.3%, in the iron-deficient group developed duodenal tumors; in the control group, only 1 of 15 rats developed a tumor (i.e., 6.6%). Also, iron-deficient rats had multiple tumors. Histological examination of the colon and duodenum revealed that the tumors were adenocarcinomatous in nature. Another notable feature in the iron-deficient group was the presence of atypical cells in the livers of carcinogen-treated iron-deficient rats. This study thus suggests that there is a greater incidence of tumors in iron deficiency and that the proximal part of the intestines seems to be the preferred site. The presence of atypical cells in the liver suggests that in iron deficiency, besides gastrointestinal tract tumors, the liver may also be a favored site for abnormalities.