Adverse effects of long-term omeprazole usage on magnesium homeostasis in male Sprague-Dawley rats
Keywords:
Adverse effect, Mg2 deficiency, Omeprazole, Mg2 homeostasisAbstract
Background: It is still debatable whether (and by what exact mechanism) prolonged use of
omeprazole causes hypomagnesemia.
Objectives: To study the effects of omeprazole on magnesium (Mg2+) homeostasis in male
Sprague-Dawley rats.
Materials and Methods: An experimental group of animals (n=24) were subcutaneously
injected with 20 mg/kg/day of omeprazole for 24 weeks. The control group of animals (n=24)
received an equivalent volume of distilled water. The animals were subcutaneously injected
with 20 mg/kg/day of omeprazole for 24 weeks. Mg2+ homeostasis was assessed throughout
the 24 week experiment at 4 week intervals (weeks 0, 4, 8, 12, 16, and 24). Intestinal and renal
Mg2+ handling was observed after oral or intravenous Mg2+ administration. Bone and muscle
Mg2+ content was measured by atomic absorption spectrophotometer. Renal magnesiotropic
protein expression was investigated with Western blot analysis.
Results: Omeprazole-treated rats showed hypomagnesemia from week 8 of the experiment.
Lower bone and muscle Mg2+content – as well as higher bone resorption – was shown in
omeprazole treated rats. Higher renal magnesiotropic protein expression was also demonstrated.
Conclusion: Omeprazole suppressed intestinal Mg2+ absorption and induced body Mg2+
depletion, thus explaining the underlying mechanism of omeprazole-induced hypomagnesemia.
References
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P, Uppal R. Effect of oral magnesium
supplementation on blood pressure,
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18: 919-26.
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Crapanzano C., Albisetti W., Maier J.A. Nitric
oxide mediates low magnesium inhibition
of osteoblast-like cell proliferation. J. Nutr.
Biochem. 2012; 23: 1224–9.
28. Belluci M.M., Schoenmaker T., RossaJunior C., Orrico S.R., de Vries T.J., Everts
V. Magnesium deficiency results in an
increased formation of osteoclasts. J.
Nutr. Biochem. 2013. doi: 10.1016/j.
jnutbio.2012.12.008.
29. Shabajee N, Lamb EJ, Sturgess I, Sumathipala
RW. Omeprazole and refractory
hypomagnesaemia. BMJ. 2008;337(7662):
a425. doi: 10.1136/bmj.39505.738981.BE
Magnesium in man: implications for health
and disease. Physiol Rev. 2015; 95: 1–46.
2. Guéroult M, Boittin O, Mauffret O, Etchebest
C, Hartmann B. Mg2+ in the major groove
modulates B-DNA structure and dynamics.
PLoS One. 2012; 7: e41704.
3. Bairoch A. The ENZYME database in 2000.
Nucleic Acids Res. 2000; 28: 304–5.
4. Shahi A, Aslani S, Ataollahi M,
Mahmoudi M. The role of magnesium
in different inflammatory diseases.
Inflammopharmacology. 2019; 27: 649-61.
5. Liu M, Dudley SC Jr. Magnesium, oxidative
stress, inflammation, and cardiovascular
disease. Antioxidants (Basel). 2020; 9: 907.
6. Chui D, Chen Z, Yu J, Zhang H, Wang W,
Song Y, Yang H; Liang Zhou. Magnesium
in Alzheimer’s disease.In: Vink R, Nechifor
M, eds. Magnesium in the Central Nervous
System. Adelaide (AU): University of
Adelaide Press; 2011.
7. Oyanagi K, Hashimoto T. Magnesium in
Parkinson’s disease: an update in clinical
and basic aspects. In: Vink R, Nechifor M,
eds. Magnesium in the Central Nervous
System. Adelaide (AU): University of
Adelaide Press; 2011.
8. Shechter M. Magnesium and cardiovascular
system. Magnes Res. 2010; 23: 60-72.
9. Castiglioni S, Cazzaniga A, Albisetti W, Maier
JA. Magnesium and osteoporosis: current
state of knowledge and future research
directions. Nutrients. 2013; 5: 3022-33.
10. Serefko A, Szopa A, Poleszak E. Magnesium
and depression. Magnes Res. 2016; 29:
112-9.
11. Mejia A, Kraft WK. Acid peptic diseases:
pharmacological approach to treatment.
Expert Rev Clin Pharmacol. 2009; 2:
295–314.
12. Patterson Burdsall D, Flores HC, Krueger
J, Garretson S, Gorbien MJ, Iacch A, Dobbs
V, Homa T. Use of proton pump inhibitors
with lack of diagnostic indications in 22
Midwestern US skilled nursing facilities. J
Am Med Dir Assoc. 2013. 14: 429–32.
13. Cundy T, Dissanayake A. Severe
hypomagnesemia in longterm users of
proton-pump inhibitors. Clin Endocrinol.
2008; 69: 338–41.
14. Cundy T, Mackay J (2011) Proton pump
inhibitors and severe hypomagnesemia.
Curr Opin Gastroenterol. 2011; 27: 180–5.
15. Danziger J, William JH, Scott DJ, Lee J,
Lehman LW, Mark RG, Howell MD, Celi LA,
Mukamal KJ Proton-pump inhibitor use
is associated with low serum magnesium
concentrations. Kidney Int. 2013; 83:
692–9.
16. Epstein M, McGrath S, Law F (2006) Protonpump inhibitors and hypomagnesemic
hypoparathyroidism. N Engl J Med. 2006;
355: 1834–6.
17. Schietzel S, Moor MB, Fuster DG. Severe
hypomagnesemia. J Nephrol. 2021; doi:
10.1007/s40620-021-01001-5.
18. Metz DC, Sostek MB, Ruszniewski P,
Forsmark CE, Monyak J, Pisegna JR.
Effects of esomeprazole on acid output
in patients with Zollinger-Ellison syndrome
or idiopathic gastric acid hypersecretion.
Am J Gastroenterol. 2007; 102: 2648-54.
19. Thongon N, Penguy J, Kulwong S,
Khongmueang K, Thongma M. Omeprazole
suppressed plasma magnesium level and
duodenal magnesium absorption in male
Sprague-Dawley rats. Pflugers Arch. 2016;
468: 1809-21.
20. S u k s r i d e c h a c i n N , K u l w o n g P ,
Chamniansawat S, Thongon N. Effect of
prolonged omeprazole administration
on segmental intestinal Mg2+ absorption
in male Sprague-Dawley rats. World J
Gastroenterol. 2020; 26: 1142-55.
21. Lameris ALL, Hess MW, van Kruijsbergen I,
Hoenderop JGJ, Bindels RJM. Omeprazole
enhances the colonic expression of the
Mg2+ transporter TRPM6. Pflugers Arch Eur
J Physiol 2013; 465: 1613–20.
22. HessMW, de Baaij JHF, Gommers LMM,
Hoenderop JGJ, Bindels RJM. Dietary inulin
fibers prevent proton-pump inhibitor
(PPI)-induced hypocalcemia in mice. PLoS
One 2015; 10: e0138881. https://doi.
org/10.1371/journal.pone.0138881.
23. Quinn R. Comparing rat’s to human’s age:
howold ismy rat in people years? Nutrition.
2005; 21: 775–7.
24. Kim TH, Jung JW, Ha BG, Hong JM, Park EK,
Kim HJ, Kim SY. The effects of luteolin on
osteoclast differentiation, function in vitro
and ovariectomy-induced bone loss. J Nutr
Biochem. 2011. 22: 8-15.
25. Kh R, Khullar M, Kashyap M, Pandhi
P, Uppal R. Effect of oral magnesium
supplementation on blood pressure,
platelet aggregation and calcium handling
in deoxycorticosterone acetate induced
hypertension in rats. J Hypertens. 2000;
18: 919-26.
26. Xiao WH, Bennett GJ. Magnesium
suppresses neuropathic pain responses in
rats via a spinal site of action. Brain Res.
1994; 666: 168-72.
27. Leidi M., Dellera F., Mariotti M., Banfi G.,
Crapanzano C., Albisetti W., Maier J.A. Nitric
oxide mediates low magnesium inhibition
of osteoblast-like cell proliferation. J. Nutr.
Biochem. 2012; 23: 1224–9.
28. Belluci M.M., Schoenmaker T., RossaJunior C., Orrico S.R., de Vries T.J., Everts
V. Magnesium deficiency results in an
increased formation of osteoclasts. J.
Nutr. Biochem. 2013. doi: 10.1016/j.
jnutbio.2012.12.008.
29. Shabajee N, Lamb EJ, Sturgess I, Sumathipala
RW. Omeprazole and refractory
hypomagnesaemia. BMJ. 2008;337(7662):
a425. doi: 10.1136/bmj.39505.738981.BE
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Published
29-12-2021
How to Cite
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Thongon N, Suksridechacin N, Wongchuen S, Chubsuwan A. Adverse effects of long-term omeprazole usage on magnesium homeostasis in male Sprague-Dawley rats. ฺBu J Med [internet]. 2021 Dec. 29 [cited 2026 Jan. 24];8(2):72-85. available from: https://he01.tci-thaijo.org/index.php/BJmed/article/view/254054
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