Table 1.
Comparison of arsenic exposure effects on the signs of MS between epidemiological studies and animal models.
| Model (species) | Arsenic dose (time) | MS-related effects | Ref. |
|---|---|---|---|
| Epidemiological studies | |||
| Taiwanese population | Arsenic in water in non-MS patients: 569.94 ± 321.51 ppb Arsenic in water in MS-patients: 684.39 ± 245.93 ppb |
↑ MS (DMA%) | (14) |
| American Indian communities | Arsenic metabolites assessed in urine Total urinary arsenic 6.5 ppb |
↑ MS (DMA%) ↑ BMI (DMA%) ↑ Fasting glucose = HDL (DMA%) = TAG (DMA%) = Hypertension (DMA%) = HOMA-IR |
(15) |
| Iranian population | Arsenic in water 257 to 342 ppb. Urinary arsenic was measured in subjects Total urinary arsenic 3 ppb |
↑ MS (DMA% and DMA/MMA) | (16) |
| Chilean population | Cumulative arsenic exposure lagged 40 years: 610–5279 ppb |
↑ Diabetes in obese individuals | (24) |
| Adult women U.S. population |
Urinary total arsenic and speciated arsenic Total urinary arsenic 6.5 ppb |
High BMI associated with lower arsenic methylation | (25) |
| Adult women Chilean population |
Urinary total arsenic adjusted for creatinine Total urinary arsenic 14 ppb |
= BMI = Fat mass percentage |
(26) |
| Bangladeshi population | Cumulative arsenic exposure lagged 10 years: >50–250 ppb |
↑ Diabetes in exposures higher than 50 ppb = BMI |
(27) |
| Korean population | Total urinary arsenic ranging from 0.36-36.7 ppb | = BMI ↓ HDL |
(28) |
| Adult Welders US Population |
Arsenic in toenails 0.18 (0.15) mg/g toenail. |
Inverse correlation between BMI and toenail arsenic | (29) |
| Non-Hispanic white, Non-Hispanic black, Mexican American and Other Hispanic populations | Urinary arsenic | Inverse correlation between excreted arsenic and BMI | (30) |
| Taiwanese population | Arsenic concentrations in water 700 to 930 ppb) |
↑ T2D = BMI |
(47) |
| Bangladeshi population | 142 ± 278 ppb water in non-T2D 202 ± 277 ppb in the water of T2D |
↑ T2D | (54) |
| Taiwanese children and adolescents | Urinary total arsenic and speciated arsenic Total urinary arsenic 27.06 ppb |
↑ HOMA-IR (higher effect of arsenic in subjects with high BMI) | (55) |
| Bangladeshi population |
Mean arsenic concentration in water of 129.5 ppb | = BMI ↑ Insulin resistance HOMA-IR ↑ Fasting blood glucose ↓ Lean body mass ↓ HOMA-B in females ↑ Hyperinsulinemia |
(56) |
| US adolescents | Urinary total arsenic and speciated arsenic Total urinary arsenic 3.77 ppb |
= HOMA-IR | (57) |
| Mexican population | Arsenic in water: 77.3 ppb in T2D 39.2 ppb in non-T2D |
↑ HbA1c ↓ Hyperinsulinemia ↓ HOMA-IR |
(58) |
| Bangladeshi population | Arsenic in drinking water 173.46 ppb | ↓ Cholesterol, LDL and HDL ↑ Oxidized LDL |
(59) |
| Chinese population | Arsenic measured in plasma (no concentrations available) | ↑ Dyslipidemia ↓ HDL |
(60) |
| Mouse models | |||
| Adult C57BL/6 male mice | Sodium arsenite 25 and 50 ppm (8 weeks) | ↑ Glucose intolerance (50 ppm) = Body weight |
(31) |
| Adult C57BL/6 male mice | Sodium arsenite 25 and 50 ppm (20 weeks) + HFD | ↓ Weight gain and adiposity (25 and 50 ppm + HFD) ↑ Liver TAG (25 ppm + HFD) ↑ Glucose intolerance (25 and 50 ppm + HFD) ↓HOMA-IR (25 and 50 ppm+ HFD) |
(32) |
| Adult C57BL/6J male mice | Sodium arsenite 50 ppm (16 weeks) + HFD | = Diet-induced body weight gain ↓ Diet-induced visceral adiposity ↓ Diet-induced liver TAG ↓ HOMA-IR ↓ HOMA-β |
(33) |
| Swiss Webster male mice in utero (IU) or in utero until adulthood (IU+) or adulthood only (PN) | Sodium arsenite 100 ppb (from in utero until post-natal week 13) | ↑ TAG in IU and IU+ ↑ Cholesterol in IU+ ↑ FFA in IU+ ↑ NAFLD in IU and IU+ ↑ Body weight in IU+ ↑ HOMA-IR in IU+ |
(37) |
| Female offspring from CD-1 mice treated in utero | Sodium arsenite 10 ppb and 42.5 ppm In utero |
↑ Body weight and adiposity (both doses) ↑ Glucose intolerance ↑ Hyperinsulinemia |
(38) |
| Adult C57BL/6J male mice | Sodium arsenite 50 ppm (8 weeks) | = Body weight ↑ Glucose intolerance = Insulin resistance (ITT) ↓ HOMA-IR |
(61) |
| Adult female and ovariectomized ICR mice | 0.05 and 0.5 ppm (6 weeks) | ↑ HOMA-IR in ovariectomized females + 0.05 and 0.5 ppm arsenic ↑ Fasting glucose ↓ Fasting insulin in sham females + arsenic ↑ Hyperinsulinemia in ovariectomized females + arsenic ↑ Insulin resistance in ovariectomized females + arsenic (ITT) ↑ Glucose intolerance in ovariectomized females + arsenic |
(62) |
| Adult NMRI male mice | Sodium arsenite 25 and 50 ppm (20 weeks) + HFD | ↓ Diet-induced body weight ↓ Diet-induced fasting glucose ↑ Glucose intolerance ↓ Diet-induced HOMA-IR ↓ Diet-induced insulin resistance (ITT) ↓ Diet-induced dyslipidemia |
(63) |
| Adult non-diabetic male C57BLKS/J db/m mice and diabetic C57BKS/Leprdb (db/db) mice | Sodium arsenite 3 ppm (16 weeks) | = Body weight gain in both mice models ↑ Fasting glucose in db/db mice + arsenic ↑ Hyperinsulinemia in db/m mice + arsenic ↓ Insulin levels in db/db mice + arsenic = HOMA-IR in both mice models ↑ Glucose intolerance in db/db mice + arsenic ↓ Insulin resistance in db/db mice + arsenic (ITT) ↑ FFA in adipose tissue |
(64) |
| Rat models | |||
| Adult male Wistar rats | Sodium arsenite 3.4 mg/kg/day (90 days) | ↑ Fasting glucose ↑ Hyperinsulinemia ↑ HOMA-IR |
(46) |
| Adult male Sprague-Dawley rats | Sodium arsenite 2.5 and 5 mg/kg/day (3 months) |
↑ Hyperinsulinemia ↑ HOMA-IR ↑ Glucose intolerance ↑ Insulin resistance (ITT) ↑ Liver TAG ↑ Non-alcoholic steatosis |
(53) |
| Adult male Sprague-Dawley rats | Sodium arsenite 2.5 and 5 mg/kg/day (5 months) | ↓ Fasting insulin | (65) |
| Adult Sprague-Dawley rats | Polluted water containing 53 ppb arsenic and 30 ppb of lead (3 months) | ↑ Glucose intolerance in females and males ↑ Hyperinsulinemia during OGTT in males ↑ HOMA-IR in males ↑ TAG in females ↑ Cholesterol and LDL in males |
(66) |
| Adult male Wistar rats | Sodium arsenite 50 ppm, 100 ppm and 150 ppm Sodium arsenate 100 ppm, 150 ppm and 200 ppm (12 weeks) |
↓ Cholesterol and HDL by arsenite ↑ Cholesterol by arsenate ↓ HDL by arsenate ↑ TAG (50 ppm arsenite and 100, 150 and 200 ppm arsenate) ↑ FFA by both arsenicals ↑ TAG in liver (arsenite 50 ppm and arsenate 150 and 200 ppm) ↓TAG in liver (arsenite 100 and 150 ppm) |
(67) |
| Adult male Wistar rats | Sodium arsenite 1.5 mg/kg/day (28 days) | = Weight gain ↑ Cholesterol and LDL ↓ HDL |
(68) |
| Adult male Wistar rats | Sodium arsenite 5 mg/kg/day (4 weeks) | ↑ Cholesterol ↑ TAG, FFA, LDL ↓ HDL ↓ Weight ↑ Heart inflammation and ROS |
(69) |
| Adult male Wistar rats | Sodium arsenite 50 ppm Sodium arsenate 50 ppm (200 days) |
↓ Weigh (arsenite) ↑ Hypertension (both arsenicals) ↑ TAG and cholesterol (both arsenicals) |
(70) |
Note that while humans are exposed to arsenic doses in the range of ppb (10-6 g/L), most animal studies are performed with doses in the range of ppm (10-3 g/L).
DMA dimethylated arsenic, FFA free fatty acids, HbA1c glycated hemoglobin, HDL high density lipoprotein, HFD high fat diet, ITT insulin tolerance test, LDL low density lipoprotein, MS metabolic syndrome, NAFLD non-alcoholic fatty liver disease, OGTT oral glucose tolerance test, ROS reactive oxygen species, T2D type 2 diabetes, TAG triglycerides. ↑ arsenic induced an increase in the indicated parameter; ↓ arsenic induced a decrease in the indicated parameter; = arsenic did not induce an effect.