Hypothyroidism and hyperthyroidism change ectoenzyme activity in rat platelets

Abstract

The purinergic system has an important role in the regulation of vascular functions. The interference of thyroid hormones in this system and in cardiovascular events has been studied in recent years. However, the mechanisms involved in vascular, purinergic, and oxidative changes in thyroid disorders are not completely understood. Therefore, the present study aimed to assess purinergic enzyme activity in platelets from rats with hypothyroidism and hyperthyroidism induced, respectively, by continuous exposure to methimazole (MMI) at 20 mg/100 mL or L‐thyroxine at 1.2 mg/100 mL in drinking water for 1 month. Results showed that rats exposed to L‐thyroxine had a significant decrease in NTPDase activity, wherein ATP hydrolysis was 53% lower and ADP hydrolysis was 40% lower. Moreover, ecto‐5′‐nucleotidase activity was decreased in both groups, by 39% in the hypothyroidism group and by 52% in the hyperthyroidism group. On the other hand, adenosine deaminase (ADA) activity was increased in hyperthyroidism (75%), and nucleotide pyrophosphatase/phosphodiesterase (NPP) activity was increased in animals with hypothyroidism (127%) and those with hyperthyroidism (128%). Our findings suggest that changes in purinergic enzyme and purine levels could contribute to the undesirable effects of thyroid disturbances. Moreover, oxidative stress and, in particular, a high level of ROS production, showed a causal relation with changes in ectonucleotidase activity and nucleotide and nucleoside levels.

The association between serum adenosine deaminase levels and Graves’ disease

“…Thus, excessive oxidative stress may be the pathophysiology basis for the occurrence of complications related to GD. Baldissarelli et al established a hyperthyroid rat model by levothyroxine administration and found that ADA activity in the platelets of the hyperthyroid rat was significantly higher than controls, and ADA levels were positively associated with ROS levels ( 25 ). Multiple studies have confirmed the correlation between serum ADA levels and ROS in a variety of diseases ( 26 ), and some studies have also confirmed that inhibition of ADA can significantly reduce the production of ROS in vivo ( 27 ).…”

Diabetes and hypertension: Pivotal involvement of purinergic signaling

“…A large body of evidence supports the pivotal role of purinergic signaling and its components, i.e., signaling molecules, enzymes, and receptors, in several diseases, including cancer [ [17] , [18] , [19] , [20] , [21] ]; inflammatory diseases [ [22] , [23] , [24] ]; cardiovascular-related diseases such as hypertension, ischemia, and atherosclerosis [ [25] , [26] , [27] ]; psychiatric and neurodegenerative diseases [ [28] , [29] , [30] , [31] , [32] ]; and diabetes [ 14 , 16 , [33] , [34] , [35] , [36] , [37] ], among others [ [38] , [39] , [40] ]. The purinergic signaling pathway constitutes a ubiquitous system of cell–cell communication and is expressed in almost every cell type [ 41 ].…”

“…In corroboration with these dysfunctions, lower CD39 expression on CD4 + regulatory T cells (Treg) is associated with metabolic factors in T1DM and T2DM patients [ 76 , 104 , 105 , 170 ]. However, Pereira and colleagues [ 38 ] showed alterations in purinergic signaling in lymphocytes of diabetic rats and point to an increase in the CD39 and ADA. The increase in CD39 can reflect the high levels of ATP, which can activate T cells by engaging P2X 7 [ 24 ], while an increase in the ADA activity reduces anti-inflammatory Ado levels [ 37 ].…”

Crosstalk between the Purinergic and Immune Systems: Implications for the Glutathione Antioxidant System in Health and Disease

“…[112] ↓ ATP, ADP, and AMP hydrolysis in serum [136] ↑ ADA activity in saliva [137] Hypo thyroidism ↓ GPx activity in serum ↑ T-SH and NPSH concentrations in platelets [116] ↑ NTPDase, 5'-NT, and ADA activities in platelets ↑ CD39 expression ↓ Ado levels in serum [116] ↑ T-SH and NPSH concentrations in serum [130] ↓ 5'-NT activity in platelets ↑ NPP activity in platelets ↑ AMP and inosine levels in serum [138] ↑ CD73 in lymphocytes [130] Crosstalk between the Purinergic and Immune Systems: Implications for the Glutathione… DOI: http://dx.doi.org/10.5772/intechopen.92881…”

“…Hyperthyroidism ↓ GPx activity in the hippocampus [131] ↓ NTPDase and 5'-NT activities in platelets ↑ ADA activity in platelets ↑ ATP, ADP, AMP, and inosine in serum ↓ Ado levels in serum [138] ↑ GPx activity in the hippocampus [132] Hypertension ↑ GPx activity in mesenteric arteries [107] ↑ NTPDase, 5'-NT, and ADA activities in platelets [105] ↓ GST activity in the kidney [133] ↑ NTPDase1, NTPDase3, and CD73 expression and activity in the cortex ↑ A2A expression in hippocampus and cortex [106] Alzheimer's disease ↓ GSH and GST activity in cortex and hippocampus [124] ↓ NTPDase, 5'-NT, and ADA activities in cortex and hippocampus [124] Table 2.…”