Effects of <i>N</i>‐acetyl‐seryl‐asparyl‐lysyl‐proline on blood pressure, renal damage, and mortality in systemic lupus erythematosus

Nakagawa, Pablo; Masjoan-Juncos, Juan Xavier; Basha, Heba; Janic, Branislava; Liao, Tang Dong; Romero, César A; Peterson, Edward L.; Carretero, Oscar A.

doi:10.14814/phy2.13084

Cited by 11 publications

(8 citation statements)

References 35 publications

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“…This finding may have been due to the time course of renal injury in SLE mice; perhaps the galantamine administration was able to decrease the severity of structural and glomerular injury in tandem with decreasing blood pressure, but glomerular basement injury continued to facilitate the loss of albumin in the urine. Additionally, the female NZBWF1 model of SLE presents variably in its phenotype, and it is not unusual for several mice from a cohort to undergo fulminant renal failure or other flare-ups of the disease, similarly to human lupus patients (44); this phenomenon may help explain the lack of significance we obtained in certain areas. Our study addresses both renal inflammation and injury in the pathogenesis and maintenance of hypertension, and supports the concept that targeting a higher, neural target that regulates inflammation (e.g., the vagus nerve) may be therapeutic, even in the context of established disease.…”

Section: 5x 10mentioning

confidence: 89%

Pharmacological potentiation of the efferent vagus nerve attenuates blood pressure and renal injury in a murine model of systemic lupus erythematosus

Pham

Wang

Mathis

2018

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent evidence suggests hypertension may be secondary to chronic inflammation that results from hypoactive neuro-immune regulatory mechanisms. To further understand this association, we used systemic lupus erythematosus (SLE) as a model of inflammation-induced hypertension. In addition to prevalent inflammatory kidney disease and hypertension, SLE patients suffer from dysautonomia in the form of decreased efferent vagal tone. Based on this, the cholinergic anti-inflammatory pathway, an endogenous vagus-to-spleen mechanism that, when activated results in decreases in systemic inflammation, may be compromised in SLE. We hypothesized that stimulation of the cholinergic anti-inflammatory pathway via pharmacological potentiation of the efferent vagus nerve would reduce inflammation and halt the development of hypertension and renal injury in SLE. Female NZBWF1 mice, an established model of murine SLE, and female control mice were treated with galantamine (4 mg/kg daily ip), an acetylcholinesterase inhibitor, or saline for 14 days. At the end of therapy, carotid catheters were surgically implanted and were used to measure mean arterial pressure before the animals were euthanized. Chronic galantamine administration attenuated both splenic and renal cortical inflammation, which likely explains why the hypertension and renal injury (i.e., glomerulosclerosis and fibrosis) typically observed in murine SLE was attenuated following therapy. Based on this, the anti-inflammatory, antihypertensive, and renoprotective effects of galantamine may be mediated through activation of the cholinergic anti-inflammatory pathway. It is possible that dysfunction of the cholinergic anti-inflammatory pathway exists in SLE at the level of the efferent vagus nerve and promoting restoration of its activity through central cholinergic receptor activation may be beneficial.

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Section: 5x 10mentioning

confidence: 89%

Pharmacological potentiation of the efferent vagus nerve attenuates blood pressure and renal injury in a murine model of systemic lupus erythematosus

Pham

Wang

Mathis

2018

American Journal of Physiology-Regulatory, Integrative and Comp

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“… 14 , 15 , 20 However, recently, we have reported that Ac-SDKP delayed the onset of hypertension in an autoimmune model of systemic lupus erythematous. 17 It is known that inflammation plays a role in blood pressure in various hypertension models, 35 , 36 and decreasing the inflammation reduces the elevated blood pressure. 35 , 37 Thus, in our study, the reduction in renal inflammation induced by Ac-SDKP could be a possible explanation for the decreased blood pressure in the HS-fed ZO rats.…”

Section: Discussionmentioning

confidence: 99%

“… 16 Recently, we have also shown that Ac-SDKP can delay the onset of hypertension in systemic lupus erythematous. 17 However, the effect of Ac-SDKP on obesity-related kidney damage and hypertension is still unknown.…”

mentioning

confidence: 99%

Renal Protective Effects of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) in Obese Rats on a High-Salt Diet

Maheshwari

Romero

Monu

et al. 2018

American Journal of Hypertension

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BACKGROUNDObesity is a public health problem, associated with salt sensitive hypertension, kidney inflammation, and fibrosis. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a tetra peptide with anti-inflammatory and anti-fibrotic properties. However, its effect on preventing kidney damage in obesity is unknown. We hypothesized that Zucker obese (ZO) rats on a high-salt (HS) diet develop renal damage, inflammation, fibrosis, and this is prevented with Ac-SDKP treatment.METHODSZucker lean (ZL) and ZO rats (8 weeks old) were treated with Ac-SDKP (1.6 mg/kg/day) while maintained on either a normal-salt (NS; 0.4%) or HS (4%) diet for 8 weeks. Systolic blood pressure (SBP), albuminuria, renal inflammation, and fibrosis were evaluated.RESULTSHS diet increased macrophage infiltration in the kidneys of both ZL and ZO rats but was significantly higher in ZO rats receiving the HS diet (ZL + NS, 13.9 ± 1.3 vs. ZL + HS, 19.14 ± 1.5 and ZO + NS, 25.5 ± 1.4 vs. ZO + HS, 87.8 ± 10.8 cells/mm2; P < 0.05). Ac-SDKP prevented macrophage infiltration in ZO rats (ZO + HS + Ac-SDKP, 32.18 ± 2.4 cells/mm2; P < 0.05). Similarly, glomerulosclerosis, cortical, and medullary interstitial fibrosis were increased in ZO rats fed the HS diet, and Ac-SDKP attenuated these alterations (P < 0.05). SBP was increased in ZO rats fed the HS diet (ZO + NS, 121.3 ± 8.9 vs. ZO + HS, 164 ± 6.9 mm Hg; P < 0.05), and it was significantly decreased with Ac-SDKP treatment (ZO + HS + Ac-SDKP, 144.05 ± 14.1 mm Hg; P = 0.004). Albuminuria was higher in ZO rats than in ZL rats; however, neither HS nor Ac-SDKP treatment affected it.CONCLUSIONSAc-SDKP treatment in ZO rats fed a HS diet prevented renal damage by reducing inflammation, fibrosis, and SBP.

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“…Kidney paraffin-embedded sections were stained using PAS staining and intraglomerular mesangial proliferation together with proximal tubule brush boarder alterations were analyzed [51,52]. A minimum of 50 renal fields per animal were observed using light microscope (Olympus, Germany) at final magnification of 400×.…”

Section: Methodsmentioning

confidence: 99%

NLRP3 Inflammasome Modulation by Melatonin Supplementation in Chronic Pristane-Induced Lupus Nephritis

Bonomini

Santos

Veronese

et al. 2019

IJMS

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Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation.

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Effects of N‐acetyl‐seryl‐asparyl‐lysyl‐proline on blood pressure, renal damage, and mortality in systemic lupus erythematosus

Cited by 11 publications

References 35 publications

Pharmacological potentiation of the efferent vagus nerve attenuates blood pressure and renal injury in a murine model of systemic lupus erythematosus

Pharmacological potentiation of the efferent vagus nerve attenuates blood pressure and renal injury in a murine model of systemic lupus erythematosus

Renal Protective Effects of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) in Obese Rats on a High-Salt Diet

NLRP3 Inflammasome Modulation by Melatonin Supplementation in Chronic Pristane-Induced Lupus Nephritis

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