Trigonelline Chloride Ameliorated Triphenyltin-Induced Testicular Autophagy, Inflammation, and Apoptosis: Role of Recovery
Source abstract
Abstract
Abstract Triphenyltin chloride (TPT-Cl) is an organometallic organotin. This study aimed to investigate the role of trigonelline (TG) along with the impact of TPT withdrawal on the testicular toxicity induced by TPT-Cl. Thirty-six adult male albino rats were divided into control, TG (40 mg/kg/day), TPT-Cl (0.5 mg/kg/day), TG + TPT-Cl, and recovery groups. Animals were daily gavaged for 12 weeks. Both TG and TPT-Cl withdrawal improved TPT-Cl-induced testicular toxicity features involving testis and relative testis weight reduction, luteinizing hormone, follicular stimulating hormone, and sex hormone-binding globulin elevation, reduction of inhibin B, free testosterone levels, and sperm count reduction with increased abnormal sperm forms. Moreover, both TG and TPT-Cl withdrawal reduced inflammatory activin A, follistatin, tumor necrosis factor α, interleukin-1β, and proapoptotic Bax and elevated antiapoptotic Bcl2 in testicular tissues mediated by TPT-Cl. TG and TPT-Cl withdrawal restored the excessive autophagy triggered by TPT-Cl via elevation of mTOR, AKT, PI3K, and P62/SQSTM1 and reduction of AMPK, ULK1, Beclin1, and LC3 mRNA gene expressions and regained the deteriorated testicular structure. In conclusion, TG and TPT-Cl withdrawal had an ameliorative role in partially reversing TPT-Cl-induced testicular toxicity. However, the findings indicated that the use of TG as an adjunctive factor is more favorable than TPT-Cl withdrawal, suggesting the capability of the testis for partial self-improvement.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Marine Biology and Environmental Chemistry · Microplastics and Plastic Pollution · Environmental Toxicology and Ecotoxicology
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Zagazig University , Zagazig 44519 , Egypt
Histology and Cell Biology Department, Faculty of Medicine, Tanta University , Tanta 31527 , Egypt
Pathology Department, Faculty of Medicine, Zagazig University , Zagazig 44519 , Egypt
Anatomy and Embryology Department, Faculty of Medicine, Zagazig University , Zagazig 44519 , Egypt
Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University , Unaizah 51911 , Saudi Arabia
Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University , Buraydah 51911 , Saudi Arabia
Department of Pathology, Faculty of Medicine, University of Benghazi , Benghazi , Libya
References (81)
Show source-provided references
1. Interleukin-1 beta enhances and interferon-gamma suppresses activin A actions by reciprocally regulating activin A and follistatin secretion from bone marrow stromal fibroblasts10.1046/j.1365-2249.2001.01644.x ↗
2. Expression of immune checkpoint regulators, cytotoxic T-lymphocyte antigen-4, and programmed death-ligand 1 in Epstein–Barr virus-associated nasopharyngeal carcinoma10.1097/PAI.0000000000000903 ↗
3. Green Coffea arabica extract ameliorates testicular injury in high-fat diet/streptozotocin-induced diabetes in rats10.1155/2020/6762709 ↗
4. The usefulness of 4 immunoperoxidase stains applied to urinary cytology samples in the pathologic stage of urothelial carcinoma: A study with histologic correlation10.1097/PAI.0000000000000905 ↗
5. Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma10.1016/j.yexmp.2021.104670 ↗
6. Prognostic and clinic-pathological significances of SCF and COX-2 expression in inflammatory and malignant prostatic lesions10.1007/s12253-018-0534-1 ↗
7. Activation of autophagy by sitagliptin attenuates cadmium-induced testicular impairment in rats: Targeting AMPK/mTOR and Nrf2/HO-1 pathways10.1016/j.lfs.2021.119031 ↗
8. Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice10.1111/andr.12222 ↗
9. Evaluation of antifibrotic effects of coffee and cocoa extracts in rats with thioacetamide-induced fibrosis10.1007/s00217-018-3119-z ↗
10. Apoptosis, necrosis and autophagy are influenced by metabolic energy sources in cultured rat spermatocytes10.1007/s10495-012-0709-2 ↗
11. Autophagy modulators in cancer therapy10.3390/ijms22115804 ↗
12. Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway10.1186/s13098-022-00798-w ↗
13. Insulin regulates macrophage activation through activin A10.1097/shk.0b013e318123e4d0 ↗
14. Therapeutic potential of Follistatin for colonic inflammation in mice10.1053/j.gastro.2004.11.063 ↗
15. The emerging roles of mTORC1 in macromanaging autophagy10.3390/cancers11101422 ↗
16. Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β10.1038/emboj.2011.398 ↗
17. Testicular toxicity of chloroxylenol in rats: Biochemical, pathological and flow cytometric study10.2147/JEP.S358571 ↗
18. Evaluation of apoptosis, proliferation, and adhesion molecule expression in trophoblastic tissue of women with recurrent spontaneous abortion and infected with Toxoplasma gondii10.1097/PGP.0000000000000683 ↗
19. Possible protective effects of CO Q10 against vincristine-induced peripheral neuropathy: Targeting oxidative stress, inflammation, and sarmoptosis10.1002/jbt.22976 ↗
20. Effects of triphenyltin chloride on implantation and pregnancy in rats10.1016/S0890-6238(97)00007-5 ↗
21. Farah · 2019
22. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy10.1128/MCB.00079-13 ↗
23. Gamble · 2008 · 12110.1016/B978-0-443-10279-0.50016-6 ↗
24. Organotins induce apoptosis by disturbance of [Ca2+] i and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes10.1006/taap.2000.9076 ↗
25. Gewirtz · 2014
26. Effects of organotin compounds on pubertal male rats10.1016/j.tox.2004.05.003 ↗
27. Autophagy and apoptosis: What is the connection?10.1016/j.tcb.2011.03.007 ↗
28. Induction of autophagy via the ROS-dependent AMPK-mTOR pathway protects copper-induced spermatogenesis disorder10.1016/j.redox.2021.102227 ↗
29. Comparison of the antioxidant activities and volatile compounds of coffee beans obtained using digestive bio-processing (elephant dung coffee) and commonly known processing methods10.3390/antiox9050408 ↗
30. Mitophagy programs: Mechanisms and physiological implications of mitochondrial targeting by autophagy10.1007/s00018-015-2087-8 ↗
31. Diverse roles for sex hormone-binding globulin in reproduction10.1095/biolreprod.111.092593 ↗
32. Fenugreek seed extract attenuates cisplatin-induced testicular damage in Wistar rats10.1111/and.12435 ↗
33. Regulation of activin and inhibin in the adult testis and the evidence for functional roles in spermatogenesis and immunoregulation10.1016/j.mce.2011.09.031 ↗
34. Is an increase in CD4/CD8 T-cell ratio in lymph node fine needle aspiration helpful for diagnosing Hodgkin lymphoma? A study of 85 lymph node FNAs with increased CD4/CD8 ratio10.1186/1742-6413-2-14 ↗
35. Masculinization of female gastropod mollusks induced by organotin compounds, focusing on mechanism of actions of tributyltin and triphenyltin for development of imposex
36. Trigonelline protects the cardiocyte from hydrogen peroxide induced apoptosis in H9c2 cells10.1016/S1995-7645(14)60328-X ↗
37. TSC2 mediates cellular energy response to control cell growth and survival10.1016/S0092-8674(03)00929-2 ↗
38. Activin A is a critical component of the inflammatory response, and its binding protein, Follistatin, reduces mortality in endotoxemia10.1073/pnas.0705971104 ↗
39. Regulation of Sertoli cell activin A and inhibin B by tumour necrosis factor α and interleukin 1α: interaction with follicle-stimulating hormone/adenosine 3,5- cyclic phosphate signalling10.1016/j.mce.2011.01.014 ↗
40. Triphenyl tin compounds as insect reproduction inhibitors10.1093/jee/58.1.4 ↗
41. The immune modulatory role of marjoram extract on imidacloprid induced toxic effects in thymus and spleen of adult rats10.1016/j.tox.2022.153174 ↗
42. Trigonellae semen enhances sperm motility and the expression of the cation sperm channel proteins in mouse testes10.1155/2015/817324 ↗
43. Expression of inhibin subunit mRNAs and inhibin levels in the testes of rats with stage-synchronized spermatogenesis10.1677/joe.0.1410131 ↗
44. Clinical application value of inhibin B alone or in combination with other hormone indicators in subfertile men with different spermatogenesis status: A study of 324 Chinese men10.1002/jcla.23882 ↗
45. Triphenyltin chloride reduces the development of rat adrenal cortex during puberty10.1016/j.fct.2020.111479 ↗
46. Trigonelline reduced diabetic nephropathy and insulin resistance in type 2 diabetic rats through peroxisome proliferator-activated receptor-γ
47. Triphenyltin chloride delays Leydig cell maturation during puberty in rats10.3389/fphar.2018.00833 ↗
48. Trigonelline inhibits caspase 3 to protect β cells apoptosis in streptozotocin-induced type 1 diabetic mice10.1016/j.ejphar.2018.08.025 ↗
49. Co-exposure to fluoride and arsenic disrupts intestinal flora balance and induces testicular autophagy in offspring rats10.1016/j.ecoenv.2021.112506 ↗
50. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method10.1006/meth.2001.1262 ↗
51. Trigonelline through the attenuation of oxidative stress exerts antidepressant- and anxiolytic-like effects in a mouse model of maternal separation stress10.1159/000503728 ↗
52. Triphenyltin disrupts the testicular microenvironment and reduces sperm quality in adult male rats10.1016/j.chemosphere.2022.134726 ↗
53. Therapeutic potential of exploiting autophagy cascade against coronavirus infection10.3389/fmicb.2021.675419 ↗
54. Regulation of germ cell and Sertoli cell development by activin, Follistatin, and FSH10.1006/dbio.2000.9625 ↗
55. Activin A balances Sertoli and germ cell proliferation in the fetal mouse testis10.1095/biolreprod.110.086231 ↗
56. Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K/Akt and MAPK signaling pathways10.1016/j.freeradbiomed.2015.11.022 ↗
57. Morphological and ultrastructural studies of human spermatogonial stem cells from patients with maturation arrest10.1111/and.12700 ↗
58. Tributyltin chloride induced testicular toxicity by JNK and p38 activation, redox imbalance and cell death in sertoli-germ cell co-culture10.1016/j.tox.2013.09.003 ↗
59. Activin-binding protein from rat ovary is Follistatin10.1126/science.2106159 ↗
60. Stem Leydig cell regeneration in the adult rat testis is inhibited after a short-term triphenyltin exposure10.1016/j.toxlet.2019.02.010 ↗
61. Triphenyltin and tributyltin inhibit pig testicular 17β-hydroxysteroid dehydrogenase activity and suppress testicular testosterone biosynthesis10.1016/j.steroids.2005.03.005 ↗
62. Okoro · 2014
63. Paternal exposure to arsenic resulted in oxidative stress, autophagy, and mitochondrial impairments in the HPG axis of pubertal male offspring10.1016/j.chemosphere.2019.07.056 ↗
64. Appropriate use of recovery groups in nonclinical toxicity studies: Value in a science-driven case-by-case approach10.1177/0300985811415701 ↗
65. Efficacy and safety of a mixed extract of Trigonella foenum-graecum seed and Lespedeza cuneata in the treatment of testosterone deficiency syndrome: A randomized, double-blind, placebo-controlled clinical trial10.5534/wjmh.170004 ↗
66. Evaluation of antioxidant and anti-inflammatory activity of green coffee beans methanolic extract in rat skin10.1080/14786419.2018.1523161 ↗
67. Significance of incorporating measures of sperm production and function into rat toxicology studies10.1530/rep.0.1210207 ↗
68. Blood levels of organotin compounds and their relation to fish consumption in Finland10.1016/j.scitotenv.2008.03.017 ↗
69. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy10.1016/j.molcel.2013.12.014 ↗
70. Effect of environmental contaminants on male reproduction10.1016/j.etap.2005.06.004 ↗
71. 4-Hydroxyisoleucine: A novel amino acid potentiator of insulin secretion10.2337/diab.47.2.206 ↗
72. The neuroprotective effect of ginsenoside Rb1 on the cerebral cortex changes induced by aluminium chloride in a mouse model of Alzheimer's disease: A histological, immunohistochemical, and biochemical study10.1016/j.jchemneu.2023.102248 ↗
73. Styne · 2016
74. Activin A stimulates IkappaB alpha/NFkappaB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors10.1002/jcb.10613 ↗
75. Male sterility in transgenic mice expressing activin betaA subunit gene in testis10.1006/bbrc.1999.0833 ↗
76. Tumour necrosis factor-alpha released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis10.1093/humrep/den240 ↗
77. Protective effect of quercetin on rat testes against cadmium toxicity by alleviating oxidative stress and autophagy10.1007/s11356-020-08947-2 ↗
78. Long-term preservation of chilled canine semen using vitamin C in combination with green tea polyphenol
79. An overview of the molecular mechanism of autophagy
80. Protective role of propolis against reproductive toxicity of triphenyltin in male rabbits10.1016/j.fct.2010.04.018 ↗
81. Protection effect of trigonelline on liver of rats with nonalcoholic fatty liver diseases10.1016/j.apjtm.2015.07.012 ↗