paymanz

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Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in <i>db/db</i> mice

Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/dbmice
Received:
14 July 2017
Accepted:
09 October 2017
Published online:
31 October 2017
Abstract


The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee’s index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, β-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more β-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.

Fat tissue around epididymis and kidneys reduced significantly after doxycycline treatment for 10 weeks (Fig. 1A). Moreover, body length increased slightly but significantly leading to decrease in Lee’s index (Fig. 1B/C), indicating that the mice turned leaner with doxycycline. The effects were obtained without losing body weight, food intake and water intake (Fig. S1).

Doxycycline reduces lipid content while increases glycogen storage in liver of db/db mice2
.
 
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paymanz

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Anti-inflammatory properties of doxycycline and minocycline in experimental models: an in vivo and in vitro comparative study. - PubMed - NCBI

AIMS AND METHODS:
Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay.

RESULTS:
In the formalin test although Mino and Dox (1, 5, 10 and 25 mg/kg, i.p.) inhibited the first phase, they acted predominantly on the second phase of the test, where inhibition of the licking time close to 80% were observed. Mino and Dox were very efficacious in reducing the carrageenan-induced paw oedema in rats (10, 25 and 50 mg/kg, i.p.) and carrageenan-induced leucocyte migration (1 and 5 mg/kg, i.p.) to mice peritoneal cavities. Besides, they also significantly inhibited MPO and LDH releases at doses ranging from 0.001 to 1 μg/ml. Thus, in general, the anti-inflammatory activity of Dox was higher as compared to that of Mino, although the radical scavenging activity of Mino was of a magnitude 10 times higher.

CONCLUSIONS:
Our data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.



Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study

Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled.

Periodontal treatment with topical antibiotics improves glycemic control in association with elevated serum adiponectin in patients with type 2 dia... - PubMed - NCBI


Periodontal treatment with topical antibiotics improves glycemic control in association with elevated serum adiponectin in patients with type 2 diabetesmellitus.
Bharti P1, Katagiri S2, Nitta H3, Nagasawa T4, Kobayashi H5, Takeuchi Y5, Izumiyama H6, Uchimura I7, Inoue S8, Izumi Y1.
Author information

Abstract
OBJECTIVES:
Chronic inflammation of periodontitis aggravates glycemic control in type 2 diabetic patients through aggravation of insulin resistance. Increased or decreased release of various inflammatory mediators, such as high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and adipokines, such as adiponectin, leptin, and resistin, are presumed to be responsible for developing and progressing insulin resistance. The purpose of this study was to examine the effects of periodontal treatment on glycemic control, seruminflammatory mediators and adipokines in type 2 diabetes patients with periodontitis.

METHODS:
Twenty-one type 2 diabetic patients with periodontitis received periodontal treatment with topicalantibiotics (intervention group) and 8 patients did not receive periodontal treatment (control group). Periodontalexamination, including probing pocket depth (PPD) and bleeding on probing (BOP), and blood sampling were performed at baseline, 2 and 6 months after periodontal treatments. Glycated hemoglobin (HbA1c), hs-CRP, TNF-α, IL-6, adiponectin, leptin, and resistin were analyzed.

RESULTS:
In the intervention group, improvements of PPD and BOP, decrease in HbA1c and elevation of serumadiponectin were observed, while in the control group, all parameters were not changed. Generalized linear model revealed that changes of serum adiponectin and TNF-α and change of BOP correlated significantly with the reduction of HbA1c at 6 months after periodontal treatments.

CONCLUSION:
The results demonstrated that periodontal treatment improves periodontal status and glycemiccontrol with elevation of serum adiponectin in type 2 diabetic patients. The results suggest that HbA1c is reduced by amelioration of insulin resistance due to elevated serum adiponectin after periodontal treatments.
 
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Yggr

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I’m wanting to try doxycycline for 3-6months for these improvements. I can only get it in 100mg capsules. Could I dose it every other day or would 1 per day be ok?
 

paymanz

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I’m wanting to try doxycycline for 3-6months for these improvements. I can only get it in 100mg capsules. Could I dose it every other day or would 1 per day be ok?
In my opinion 1 per day is probably to much. And its better if open the capsule and divide it into 2-3 doses and take a dose per day.

A 100mg dose upsets my stomach a bit.
 

benaoao

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At this point it looks like it’s always the same story since the body functions as a whole. That’s why I don’t even care about super extensive blood tests anymore. Monitor body fat, blood glucose and body temperature and whatever it is you’re doing is probably the good approach
 

raysputin

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I’m taking 100mg minocycline per day for ten days. I don’t really notice anything from it. It doesn’t even give me a stomach ache if I take it with coffee and no food in the morning. What could be up with my gut?
 
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