Anat Cell Biol.  2021 Jun;54(2):241-248. 10.5115/acb.20.230.

Microscopic features of the rat adrenal gland associated with chronic codeine phosphate administration

• Ongidi IH
• Abdulsalaam FY
• Amuti TM
• Kaisha WO
• Awori KO
• Pulei AN

• KMID: 2516908
• DOI: http://doi.org/10.5115/acb.20.230

Abstract

Codeine is an opioid analgesic and antitussive that has been widely abused. Some adverse effects noted with its abuse include adrenocortical insufficiency and activation of the hypothalamic-pituitary-adrenal axis. The structural basis for these dysfunctions is not clearly understood. Twenty-five adult male rats were used for the study. They were divided into intervention and control groups that were administered 40 mg/kg of codeine phosphate and normal saline respectively by gavage daily for 50 days. Subsequently, both groups were given normal saline for a further fourteen days to note recovery changes. At day 0, 50 and 64, rats were randomly selected from both groups, euthanized and adrenal glands harvested for histological processing and analysis. At day 50 of codeine administration, the adrenal glands demonstrated an increase in zona fasciculata thickness but a decrease in zona reticularis thickness. Lower values were noted in the volume density of zona reticularis and cells count of the medulla in the experimental compared to the control groups (P-value<0.05). The experimental group also showed an increase in vascularization and connective tissue in the glands. After 14 days of recovery, most of the changes observed in experimental animals were reversed and the adrenal glands in both groups had similar features. A decrease in cell count of the adrenal medulla was however observed (P-value<0.05). In conclusion administration of codeine phosphate causes discernible changes in the microscopic structure of the adrenal gland, most of which appear to be reversed after two weeks recovery period.

Keyword

Codeine; Adrenal glands; Opioid; Opioid-related disorders

Figure

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  Fig. 1 Light microscopic features of the adrenal gland in the 50 days control and experimental groups. (A) Adrenal cortex and medulla in the 50 days control group. Notice the similar proportions of ZF and ZR in the cortex (H&E, ×100). (B) Adrenal cortex and medulla in the 50 days experimental group. Notice the increase in zona fasciculata thickness compared to the other cortical zones (H&E, ×100). (C) The capsule, ZG and zona fasciculata in the 50 days control group at higher magnification. Notice that the cells are densely arranged, the arrows show vascular sinusoids (H&E, ×400). (D) The capsule, zona glomerulosa and zona fasciculata in the 50 days experimental group at higher magnification. Notice the increased thickness of the capsule and the increased vascular spaces (arrowheads) compared to the control (H&E, ×400). (E) The zona reticularis and medulla in the 50 days control group at higher magnification. Notice that cells of zona reticularis are arranged in anastomosing cords (asterisk), the arrows show vascular sinusoids (H&E, ×400). (F) The zona reticularis and medulla in the 50 days experimental group at higher magnification. Notice the vesicular nuclei (arrows) in the medullary cells and smaller vascular spaces compared to the control (H&E, ×400). Asterisk, veins; BV, blood vessel; C, capsule; MED, medulla; ZF, zona fasciculata; ZG, zona glomerulosa; ZR, zona reticularis.

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  Fig. 2 Light microscopic features of the adrenal gland in the 14-day recovery control and experimental groups. (A) The drenal cortex and medulla in the 14-day recovery control group (H&E, ×100). (B) The adrenal cortex and medulla in the 14-day recovery experimental group. Notice relative thickness of the three cortical zones is similar to the control group (H&E, ×100). (C) The capsule, zona glomerulosa and zona fasciculata in the 14-day recovery control group at higher magnification. Arrows show the capsule (H&E, ×400). (D) The capsule, zona glomerulosa and zona fasciculata in the 14-day recovery experimental group at higher magnification. The thickness of the capsule is similar to the control. Arrows show the capsule (H&E, ×400). (E) The zona reticularis and medulla in the 14-day recovery control group at higher magnification (H&E, ×400). (F) The zona reticularis and medulla in the 14-day recovery experimental group at higher magnification. The features are comparable to the control group (H&E, ×400). C, capsule; MED, medulla; ZF, zona fasciculata; ZG, zona glomerulosa; ZR, zona reticularis.

Reference

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