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. 2025 Jun 27;51(1):241.
doi: 10.1007/s00068-025-02915-6.

Protective effects of tasimelteon on kidney injury in a traumatic brain injury rat model: a histopathological and immunohistochemical study

Adem Milletsever  1 , Halil Asci  2   3 , Rumeysa Taner  3 , Ozlem Ozmen  4
Affiliations

Protective effects of tasimelteon on kidney injury in a traumatic brain injury rat model: a histopathological and immunohistochemical study

Adem Milletsever et al. Eur J Trauma Emerg Surg. .

Abstract

Purpose: Traumatic brain injury (TBI) is a condition characterized by structural and functional damage to the brain following trauma and is a significant cause of mortality. Acute kidney injury (AKI) has been reported in patients with TBI and is a commonly encountered complication. This study examines the effect of tasimelteon (Tasi) application on kidney tissue in TBI rats by histopathological and immunohistochemical staining.

Methods: Forty male Wistar Albino rats weighing 300–350 g were randomly divided into four groups: Control group, Trauma group (Trau), Trau-Tasi-1 group (trauma-1 mg/kg Tasi intraperitoneally), and Trau-Tasi-10 group (trauma-10 mg/kg Tasi intraperitoneally). At the end of the experimental phase, after euthanasia, kidney tissue was collected for histopathological and immunohistochemical analyses.

Results: The results of histopathological and immunohistochemical staining demonstrate that brain trauma may induce kidney injury, while Tasi possesses the potential to ameliorate kidney lesions associated with TBI. It has been found that Trau-Tasi-10 is more effective in treatment compared to Trau-Tasi-1.

Conclusion: We observed Tasi’s kidney injury ameliorating activity in TBI rats through histopathological and immunohistochemical staining findings.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00068-025-02915-6.

Keywords: Brain; Kidney; Pathology; Tasimelteon; Trauma.

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Conflict of interest statement

Declarations. Ethical approval: All animal experiments and animal research were conducted in accordance with the animal research guidelines specified in the ARRIVE 2.0 Guide. The procedures conducted on rats were reviewed and approved by the Animal Experiments Local Ethics Committee of Suleyman Demirel University (Ethic No: 12.12.2024/15–415). Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study Design and Trauma Set-up. Trau-Tasi-1 group: Trauma-Tasimelteon 1 mg/kg group; Trau-Tasi-10 group: Trauma-Tasimelteon 10 mg/kg group
Fig. 2
Fig. 2
Histopathological appearance of the kidney between the groups. (A) Normal tissue histology in the Control group. (B) Proteinous fluid in the tubular lumens (arrows) in the Trau group. (C) Decreased pathological findings in the Trau-Tasi-1 group. (D) Marked amelioration in the Trau-Tasi-10 group. HE, Scale Bars = 50 μm. Graphs display the statistical analysis of histopathological scores. Values are presented as the mean ± SD. Abbreviations: Cont: Control, Trau: Trauma, Tas-1: Tasimelteon 1 mg/kg, Tasi-10: Tasimelteon 10 mg/kg, ***:p < 0.001 *:p < 0.05
Fig. 3
Fig. 3
Representative haptoglobin immunohistochemical findings among the groups. (A) Negative expressions in the Control group. (B) Marked increased expressions (arrows) in the Trau group. (C) Markedly decreased expressions in the Trau-Tasi-1 group. (D) No expression in the Trau-Tasi-10 group. Streptavidin Biotin Peroxidase Method, Scale Bars = 50 μm. Trau: Trauma, Trau-Tas-1: Tasimelteon 1 mg/kg, Trau-Tasi-10: Tasimelteon 10 mg/kg
Fig. 4
Fig. 4
Representative malondialdehyde immunohistochemical findings among the groups. (A) Negative expressions in the Control group. (B) Marked increased expressions (arrows) in the Trau group. (C) Markedly decreased expressions in the Trau-Tasi-1 group. (D) No expression in the Trau-Tasi-10 group. Streptavidin Biotin Peroxidase Method, Scale Bars = 50 μm. Trau: Trauma, Tas-1: Tasimelteon 1 mg/kg, Tasi-10: Tasimelteon 10 mg/kg
Fig. 5
Fig. 5
Representative TRPM-2 immunohistochemical findings among the groups. (A) Negative expressions in the Control group. (B) Marked increased expressions (arrows) in the Trau group. (C) Markedly decreased expressions in the Trau-Tasi-1 group. (D) No expression in the Trau-Tasi-10 group. Streptavidin Biotin Peroxidase Method. Scale Bars = 50 μm. TRPM-2: Transient receptor potential cation channel subfamily M member 2, Trau: Trauma, Trau-Tas-1: Tasimelteon 1 mg/kg, Trau-Tasi-10: Tasimelteon 10 mg/kg
Fig. 6
Fig. 6
Statistical analysis of immunohistochemical expressions. Graphs display the statistical analysis of Cas-3 immunoscores. Data presented as the mean ± SD. Abbreviations: Cont: Control; Trau: Trauma; Trau-Tas-1: Tasimelteon 1 mg/kg; Trau-Tasi-10: Tasimelteon 10 mg/kg. *:p < 0.05, **p < 0.01, ***:p < 0.001
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