Table 2.

Organ systems of animal models affected by dexamethasone treatment: symptoms and sequelae

Organ system affected	Symptom/sequela	Species	Dosage	Onset time	Pathogenic mechanism	References
Musculoskeletal system	Osteoporosis	Female mice (BALB/c)	1 mg/kg/day × 3 weeks	3 weeks	Osteocalcin decrease and leptin increase	[62]
		Female rats (Sprague-Dawley)	0.6 mg/kg/3 days × 12 weeks	12 weeks	Biglycan, LRP5, OPG and RUNX2 downregulation; Col1α1 upregulation	[68]
	Skeletal muscle atrophy	Female mice (Kun-Ming)	20 mg/kg/day × 8 days	8 days	Myostatin promoter activity upregulation	[73]
		Male mice (C57BL/J)	5 mg/kg/day × 18 days	6 days	Activation of AMPK/FOXO3/agtrogenes signaling	[77]
Cardiovascular system	Hypertension	Male rats (Fisher 344)	0.03, 0.3 or 3 mg/kg/day × 10 days	8, 6 or 5 days	Increased transcription of TH	[84]
		Male rabbits (New Zealand)	1000 mg/kg	Within 6 weeks	Increased transmembrane Ca2+ in VSM	[85]
		Neonatal rats (Wistar)	0.5 mg/kg + 0.3 mg/kg + 0.1 mg/kg	3 months	-	[127]
		Male rats (Wistar)	1.5 mg/kg/day × 8 days	2 days	Impaired expression of CBS and CSE	[90]
	Cardiac hypertrophy	Female neonatal rats (Wistar)	0.5 mg/kg + 0.3 mg/kg + 0.1 mg/kg	45 weeks	Increased promoter methylation in the CcnD2 gene	[94, 96]
		Neonatal rats (Wistar)	0.5 mg/kg + 0.3 mg/kg + 0.1 mg/kg	Within 15 months	-	[127]
	Arrhythmias	Male rats (Wistar)	2 mg/kg/day × 7 days	1 week	Increased ROS generation	[103]
	Diastolic dysfunction	Male rats (Wistar)	35 mg/kg/day × 15 days	15 days	Impaired calcium handling and calcineurin signaling pathway activation	[102]
Ocular system	Glaucoma	Mice (C57BL/6)	0.1% × (~ 20 μl) × 3 times/day × 20 weeks	20 weeks	Myocilin, actin and ECM proteins increase	[110]
Digestive system	Gastric ulceration	Male rats (Wister)	1 mg/kg	26 h	Inhibit prostaglandin synthetase and peroxidase	[121]
Renal system	Chronic progressive glomerulonephritis	Neonatal rats (Wistar)	0.5 mg/kg + 0.3 mg/kg + 0.1 mg/kg	Within 15 months	-	[127]
	Glomerulosclerosis			32 weeks	Accumulation of inflammatory factors	[128]
	Renal fibrosis
	Reduction of nephron			8 and 24 weeks
				4 weeks	Suppression of mitotic activity	[129]
Nervous system	Anxiety	Male albino mice	10 mg/kg	0.5 h	Dysregulation of the HPA axis	[136]
		Male rats (Sprague-Dawley)	5 mg/kg/day × 7 days	1 week	Excessive CREB phosphorylation and BDNF upregulation	[138]
	Depressive behavior	Male mice (C57BL/6 J)	4 mg/kg/day × 21 days	20 days	GR mRNA decrease	[137]
		Male mice (ICR)	60 mg/kg/day × 21 days	22 days	GR protein expression reduction	[143]
	Cerebral edema	Male rats in SE (Sprague-Dawley)	2 mg/kg	2 days	-	[150]
		Rats with acidosis (Sprague-Dawley)	3 mg/kg	4 h	AQP-1–mediated pathways	[151]
Endocrine system	Adrenocortical atrophy	Female rats (Wistar)	0.15 mg/kg/day × 7 days	Within 1 week	Inhibition of ACTH synthesis and secretion	[160]
	Hyperglycemia	Mice (C57BL/6 J)	1 mg/kg/2 days × 2 months	Within 2 months	GR/KLF9/PGC1α signaling pathway	[181]
	Diabetes	Rats (Wistar)	5 mg/kg/day × 24 days	Within 5 days	Insulin resistance	[182]
		Female rats Zucker (fa/fa)	0.2–0.4 mg/kg × 24 days	Promptly

LRP-5 low-density lipoprotein5, OPG osteoprotegerin, RUNX2 runt-related transcription factor 2, AMPK AMP-activated protein kinase, FOXO3 forkhead box O 3, TH tyrosine hydroxylase, VSM vascular smooth muscle, CBS cystathionine-β-synthase, CSE cystathionine-γ-lyase, CcnD2 gene cyclinD2 gene, ROS reactive oxygen species, ECM extracellular matrix, HPA hypothalamic-pituitary-adrenal, CREB anti-cAMP responsive element binding protein, BDNF brain-derived neurotrophic factor, GR glucocorticoid receptor, SE status epilepticus, AQP-1 aquaporin-1, ACTH adreno-cortico-tropic-hormone, KLF9 Krüppel-like factor 9, PGC1α peroxisome proliferator-activated receptor γ coactivator 1 α