Age-related glomerular lesions with albuminuria in male cotton rats

Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Otani, Yuki; Hosotani, Marina; Masum, Abdul; Islam, Rashedul; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

doi:10.1007/s00418-019-01824-1

Cited by 5 publications

(8 citation statements)

References 26 publications

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“…Plasma Cr is a more specific factor than urea level to evaluate kidney function; because Cr has all the features needed for a perfect filtration indicator. It was revealed that elevation of urea and plasma Cr along with a reduction of plasma albumin level occurs in nephropathy (23). The increase of BUN and Cr levels are related to glomerular filtration dysfunction caused by DG.…”

Section: Discussionmentioning

confidence: 99%

D-Galaktoz ile İndüklenen Farelerde Yaşlanma Modelinin Nefropatisi Üzerine Mirisitrin ve Vitamin E’nin Koruyucu Etkileri

Radmehr

Ahangarpour

Khorsandi

et al. 2021

Düzce Tıp Fakültesi Dergisi

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Aim: Aging occurs in cells and tissues due to oxidative stress in physiological conditions. D-galactose (DG) is widely used to cause aging in animal studies. In this study, the renal protective effects of myricitrin and vitamin E in the aging mice model induced by DG was evaluated. Material and Methods: Subcutaneous DG injection was used for induction of the aging model. 72 female mice were randomly divided into six groups: All groups were received DG at 500 mg/kg/d for six weeks. In the last 28 days, the groups treated with myricitrin subcutaneously received 5, 10, and 20 mg/kg/d, and the vitamin E group received 100 mg/kg/d by gavage. Urine and plasma albumin, BUN, creatinine levels, MDA, TAC, and kidney histological changes were evaluated. Results: Plasma albumin was significantly decreased (p=0.001), but a significant increase in urine albumin (p=0.001), BUN (p<0.001), and creatinine (p=0.010) levels was observed in the DG group when compared with the control. Also, a significant increase in MDA levels (p=0.002) along with a significant decrease in TAC (p=0.012) was observed. Histopathological changes such as congestion of erythrocytes (p<0.001), infiltration of inflammatory cells (p<0.001), and proximal tubule cell damage (p=0.004) significantly increased, while glomerulus diameter significantly decreased (p=0.038) in comparison to the control. Administration of myricitrin and vitamin E showed a significant ameliorative effect on all studied variables. Conclusion:The improvement effects of myricitrin on DG-induced kidney damage was approximately equivalent to vitamin E. Myricitrin and vitamin E could have beneficial effects on the nephropathy of aging model.

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Section: Discussionmentioning

confidence: 99%

D-Galaktoz ile İndüklenen Farelerde Yaşlanma Modelinin Nefropatisi Üzerine Mirisitrin ve Vitamin E’nin Koruyucu Etkileri

Radmehr

Ahangarpour

Khorsandi

et al. 2021

Düzce Tıp Fakültesi Dergisi

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“…In addition to NPH, cotton rats have noticeable unique phenotypes in the urinary, circulatory, reproductive, digestive, and integumentary systems, including systemic pathological phenotypes, such as chronic kidney disease and metabolic disorders. [10][11][12][13][14] Thus, cotton rats might also be useful for researching the comorbidities of NPH in other diseases. In conclusion, cotton rats may serve as a novel and useful model for elucidating the pathomechanism of hydrocephalus, particularly idiopathic NPH.…”

Section: Discussionmentioning

confidence: 99%

“…We here report that cotton rats have noticeable systemic pathological phenotypes, such as chronic kidney disease with anemia, metabolic disorders, and false caudal autotomy. [10][11][12][13][14] Additionally, these species possess unique phenotypes in endocrine, reproductive, and digestive organs, [15][16][17][18] suggesting that cotton rats might be useful experimental animal models. However, the central nervous system (CNS) of cotton rats has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms

et al. 2021

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Normal-pressure hydrocephalus (NPH) is a condition in which the ventricle is enlarged without elevated cerebrospinal fluid pressure, and it generally develops in later life and progresses slowly. A complete animal model that mimics human idiopathic NPH has not yet been established, and the onset mechanisms and detailed pathomechanisms of NPH are not fully understood. Here, we demonstrate a high spontaneous prevalence (34.6%) of hydrocephalus without clinical symptoms in inbred cotton rats (Sigmodon hispidus). In all 46 hydrocephalic cotton rats, the severity was mild or moderate and not severe. The dilation was limited to the lateral ventricles, and none of the hemorrhage, ventriculitis, meningitis, or tumor formation was found in hydrocephalic cotton rats. These findings indicate that the type of hydrocephalus in cotton rats is similar to that of communicating idiopathic NPH. Histopathological examinations revealed that the inner granular and pyramidal layers (layers IV and V) of the neocortex became thinner in hydrocephalic brains. A small number of pyramidal cells were positive for Fluoro-Jade C (a degenerating neuron marker) and ionized calcium-binding adaptor molecule 1 (Iba1)-immunoreactive microglia were in contact with the degenerating neurons in the hydrocephalic neocortex, suggesting that hydrocephalic cotton rats are more or less impaired projections from the neocortex. This study highlights cotton rats as a candidate for novel models to elucidate the pathomechanism of idiopathic NPH. Additionally, cotton rats have some noticeable systemic pathological phenotypes, such as chronic kidney disease and metabolic disorders. Thus, this model might also be useful for researching the comorbidities of NPH to other diseases.

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“…However, it remains unknown as to the mechanisms underlying this sex difference. Given the essential role of podocytes in glomerular filtration barrier integrity [ 24 ], and considering that Arg-II may potentially be upregulated in injured podocytes [ 23 ], this work aimed to investigate whether Arg-II is elevated with aging in podocytes, contributing to the age-associated increase in albuminuria in a natural aging mouse model.…”

Section: Introductionmentioning

confidence: 99%

Elevation of Arginase-II in Podocytes Contributes to Age-Associated Albuminuria in Male Mice

Ajalbert

Brenna

Ming

et al. 2023

IJMS

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One of the manifestations of renal aging is podocyte dysfunction and loss, which are associated with proteinuria and glomerulosclerosis. Studies show a male bias in glomerular dysfunction and chronic kidney diseases, and the underlying mechanisms remain obscure. Recent studies demonstrate the role of an age-associated increase in arginase-II (Arg-II) in proximal tubules of both male and female mice. However, it is unclear whether Arg-II is also involved in aging glomeruli. The current study investigates the role of the sex-specific elevation of Arg-II in podocytes in age-associated increased albuminuria. Young (3–4 months) and old (20–22 months) male and female mice of wt and arginase-II knockout (arg-ii−/−) were used. Albuminuria was employed as a readout of glomerular function. Cellular localization and expression of Arg-II in glomeruli were analyzed using an immunofluorescence confocal microscope. A more pronounced age-associated increase in albuminuria was found in male than in female mice. An age-associated induction of Arg-II in glomeruli and podocytes (as demonstrated by co-localization of Arg-II with the podocyte marker synaptopodin) was also observed in males but not in females. Ablation of the arg-ii gene in mice significantly reduces age-associated albuminuria in males. Also, age-associated decreases in podocyte density and glomerulus hypertrophy are significantly prevented in male arg-ii−/− but not in female mice. However, age-associated glomerulosclerosis is not affected by arg-ii ablation in both sexes. These results demonstrate a role of Arg-II in sex-specific podocyte injury in aging. They may explain the sex-specific differences in the development of renal disease in humans during aging.

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Age-related glomerular lesions with albuminuria in male cotton rats

Cited by 5 publications

References 26 publications

D-Galaktoz ile İndüklenen Farelerde Yaşlanma Modelinin Nefropatisi Üzerine Mirisitrin ve Vitamin E’nin Koruyucu Etkileri

D-Galaktoz ile İndüklenen Farelerde Yaşlanma Modelinin Nefropatisi Üzerine Mirisitrin ve Vitamin E’nin Koruyucu Etkileri

Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms

Elevation of Arginase-II in Podocytes Contributes to Age-Associated Albuminuria in Male Mice

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