Hyperthyroidism exacerbates ischemic reperfusion injury in the kidney.

Abstract

Thyroid hormones are critical regulators of vertebrate development and metabolism. Under hyperthyroid conditions, excess thyroid hormones induce expression of several enzymes and activities via activation of ligand-bound thyroid hormone receptors (TRs). Arginase (ARG) is downstream of a ligand-bound TR and overexpression of ARG2 induces the production of reactive oxygen species and subsequent exacerbation of kidney ischemia/reperfusion (I/R) injury. To clarify the association between I/R-induced kidney injury and hyperthyroidism, mice were pretreated with L-thyroxine (LT4) or vehicle alone, then subjected to I/R. Proximal tubular cell-specific conditional knockout of thyroid hormone receptor β (TRβcKO) mice was generated and the effects of I/R were analyzed. Hyperthyroidism enhanced tubular damage and fibrosis in the kidneys of mice after I/R. Hyperthyroidism induced tubular cell necroptosis following inflammatory cell accumulation in the kidney after I/R. ARG2 expressions and reactive oxygen species accumulated in the kidneys of hyperthyroid mice after I/R, but these changes were ameliorated in the kidneys of TRβcKO mice. Hyperthyroidism-enhanced kidney injury was ameliorated in the kidney of TRβcKO mice after I/R. These results suggest that excess thyroid hormones are disadvantageous for the kidney under ischemic stress. Overt hypothyroidism represents a severe thyroid hormone deficiency disease that requires LT4 treatment, while overreplacement or iatrogenic thyrotoxicosis might cause kidney injury.

• Authors: Yasuno Yamaguchi, Kohei Uchimura, Kazuya Takahashi, Toshihisa Ishii, Shunichiro Hanai, Fumihiko Furuya
• Journal: Endocrine journal (Endocr J) Vol. 69 Issue 3 Pg. 263-272 (Mar 28 2022) ISSN: 1348-4540 [Electronic] Japan
• PMID: 34629337 (Publication Type: Journal Article)

Chemical References

• Thyroid Hormones

Topics

• Animals
• Hyperthyroidism (complications, genetics)
• Hypothyroidism (metabolism)
• Kidney (metabolism)
• Mice
• Reperfusion Injury (complications, metabolism)
• Thyroid Hormones (metabolism)